Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04315350 |
| Other study ID # |
H-19017550 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2019 |
| Est. completion date |
June 11, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
University Hospital, Gentofte, Copenhagen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this study is to investigate whether ingestion of curcumin will prevent hepatic
insulin resistance (assessed by homeostatic model assessment of insulin resistance (HOMA-IR))
induced by short-term oral glucocorticoid (prednisolone) administration in overweight and
obese participants. As a secondary endpoint it will be investigated if prednisolone
administration induce or worsen the degree of NAFLD in overweight or obese participants using
magnetic resonance (MR) spectroscopy (MRS), and if curcumin can ameliorate this effect. Also,
the possible anti-inflammatory effect of curcumin will be elucidated as a range of
inflammatory markers before and after intervention will be measured. Thus, prednisolone
treatment is used as a model of development of pre-diabetes.
Description:
AIMS OF STUDY The aim of this study is to investigate whether ingestion of curcumin will
prevent hepatic insulin resistance (assessed by homeostatic model assessment of insulin
resistance (HOMA-IR)) induced by short-term oral glucocorticoid (prednisolone) administration
in overweight and obese participants.
BACKGROUND The increasing incidence and prevalence of obesity and its comorbidities calls for
research in preventing these diseases. The progression to insulin resistance and increased
blood sugar levels (i.e. prediabetes) and ultimately type 2 diabetes (T2D) in obesity is
believed to be caused by various factors of which low-grade inflammation in adipose tissue
and skeletal muscle tissue seems to inflict insulin resistance initiating metabolic
deterioration towards the type 2 diabetic phenotype. Curcumin, a polyphenolic compound that
can be extracted from the turmeric root, have been shown to exert anti-inflammatory
properties in both in vitro and animal studies. Furthermore, animal studies indicate that
curcumin is a modulator of gut microbiota composition in a metabolic beneficial direction.
Studies have shown positive results in terms of lowering hepatic insulin resistance with
curcumin in rodents and humans (measured by HOMA-IR), and another clinical trial has shown
that curcumin can prevent worsening of HOMA-IR and development of T2D in a prediabetic
population.
Glucocorticoids are a group of frequently used compounds, prescribed for a wide range of
diseases and have severe metabolic side effects as insulin resistance, T2D and non-alcoholic
fatty liver disease. Interestingly, curcumin, a phenolic compound extracted from the turmeric
root, and curcumin analogues have been shown to ameliorate glucocorticoid-induced
'dysmetabolism' in rodent studies, but no human data exist. Also, results from both in vitro
and in vivo studies with curcumin have shown promising effects in preventing NAFLD
development, but solid human data are missing. Because of the temporary effects on glucose
metabolism, short-term treatment with glucocorticoids can be used as an investigative model
of these metabolic changes. Previous studies from the research unit performing the current
study, used this setup to investigate changes in glucose homeostasis, incretin hormones and
insulin resistance. Two different mouse studies indicate that curcumin could be beneficial in
terms of preventing the metabolic changes associated with systemic glucocorticoid treatment,
but no human studies have investigated if curcumin can prevent glucocorticoid-induced
increase in HOMA-IR.
The aim of the study is to investigate the effects of curcumin of the metabolic changes
caused by short-term systemic prednisolone in a double-blinded, placebo-controlled trial in
overweight and obese individuals.
STUDY DESIGN
Participants 27 overweight and obese individuals without diabetes
METHODS
In this randomised, double-blinded, placebo-controlled trial, eligible participants will
undergo baseline assessments before being randomised to one of the following interventions:
1) Two tablets of curcumin (each tablet containing 100 mg curcumin) twice daily in 11 days
and 50 mg of prednisolone once daily in 10 days (capsule); 2) two tablets of placebo-curcumin
twice daily in 11 days and 50 mg of prednisolone once daily in 10 days (capsule); 3) two
tablets of placebo-curcumin twice daily in 11 days and one capsule of placebo-prednisolone
once daily in 10 days. In the end of the 11-day intervention period, end-of-intervention
assessments (similar to baseline assessments) will be performed. If necessary, a follow-up
visit will be made.
Information meeting and screening Prior to any protocol-related procedures, an information
meeting will be arranged, and participants will be informed of the possibility of bringing a
person of own choice to the visit. The information meeting is performed in undisturbed and
confidential surroundings. The room is reserved for this purpose, and nobody will interfere
during the meeting. It is not possible for other employees in the department to look into the
room. During this meeting, a member of the research group will explain the purpose,
procedures and possible risks of the study. The member of the research group will have proper
qualifications in terms of medical knowledge, insights in the specific project and
communications skills. It is firstly pointed out that the project is a biomedical trial.
After this, an oral information about the project is given based on the written information.
Questions will be answered as thoroughly as possible. The participant will be informed that
it is possible to have a minimum of 48 hours to evaluate participation from oral information
is given. If he does not want time to evaluate the participation, the informed consent can be
obtained. If he wants time to evaluate participation, a new meeting will be arranged with a
minimum of 48 hours from the information meeting. When the informed consent has been
obtained, screening can be done, either the same day or another day, but with a maximum of
four weeks after obtaining the informed consent. The participant will be informed that it is
possible to withdraw the written consent at any time prior to or during the study. In the
case that significant information about the participants health is found during the trial,
the participant will be able to decline having this information. Information about this
choice is confirmed in the informed consent form.
If the participant wants to know about the results of the trial and the possible consequences
for the participant, he will have the rights to get this information after the end of the
study At screening, height and body weight will be measured, medication and medical history
will be recorded, blood will be sampled for assessment of plasma/serum concentrations of
thyroid-stimulating hormone, creatinine, creatine kinase, electrolytes, aspartate
aminotransferase (ASAT), alanine aminotransferase (ALAT), lactate dehydrogenase, alkaline
phosphatase, albumin, bilirubin, gamma-glutamyltransferase, viral hepatitis markers, platelet
count, ferritin and haemoglobin, and albumin-creatinine ratio in the urine will be measured.
A physical examination will be made including evaluation of blood pressure and pulse rate.
Alcohol habits will be evaluated based on The Alcohol Use Disorder Identification Test
(AUDIT) questionnaire and quantification of the weekly amount of alcohol. An MR safety
checklist will be completed, and an MR information sheet will be given. If all inclusion
criteria and none of the exclusion criteria are met, dates for baseline assessments and
randomisation visit will be planned within 6 weeks from the screening visit. The participant
will be instructed not to consume curcumin-containing food on a daily basis from screening
until end of trial.
Baseline assessments and randomisation visit
If the participant is included during COVID19 pandemic, a phone call is done the day before
the visit to ask about recent symptoms of infection, contacts to people with COVID19 symptoms
or people with positive test for COVID19.
Included individuals will undergo an MRS of the liver (scheduled as close as possible to the
randomisation visit). Before intervention start, both randomisation visit and MRS will be
performed. For MRS, participants are placed in a horizontal position. During the MRS, a
spectroscopy of the liver will be assessed, and an estimation of visceral adipose tissue and
subcutaneous adipose tissue will be done.
During the last week before randomisation, the subject will collect a stool sample for the
determination of gut bacteria count and subtype. Stool samples will be collected by the
participant at home. Prior to defaecation a disposable collector will be placed in the toilet
from where stool will be transferred to a tube that immediately is transferred to a transport
container and placed at -20°C in the patient's freezer. Prior to transport to Gentofte
Hospital, the transport container is transferred to the cooler bag and at arrival at Gentofte
Hospital the transport container (with the sample tube) is immediately stored in at -80°C for
later analysis. This entails DNA extraction, library preperation, MiSeq 16S rRNA sequencing
and microbiota analysis (relative abundance, alpha/beta diversity, link to phenotype of
interest).
On the randomisation visit, the participant will meet in the laboratory around 8 a.m. after
10 hours of fast (including any medication) and refrainment from tobacco or nicotine
supplements use. The participant is allowed to drink water until 8 hours before meeting in
department. Furthermore, the participant will be requested to avoid heavy alcohol intake
(more than 5 units of alcohol per day) and strenuous exercise two days prior to the visit and
instructed to use non-strenuous methods of transportation to the research facility. The
following procedures will be conducted:
If the test day is during COVID19 pandemic, the participant is tested for Sars-Cov2 with a
swab procedure in the oropharynx, for immidiate PCR analysis.
1. A fasting urine sample will be collected, and the participant is asked to empty the
urinary bladder completely
2. Fasting blood samples will be collected (bone markers, serum markers of muscle
breakdown, biomarkers of NASH and fibrosis, fibroblast growths factors, triglycerides,
cholesterols, liver parameters, HbA1c, inflammatory markers, adipokines, creatinine,
haemoglobin) amounting 25 ml.
3. FibroScan: The participant will be lying in a supine position for approximately 10
minutes during which a probe using shear-waves and ultrasound is applied in the right
side of the body below the ribs.
4. Measurement of blood pressure, heart rate, body weight and hip and waist circumference.
5. A questionnaire is handed out regarding calorie intake and physical activity the day
prior to randomisation
6. IOP is measured with icare ic100 tonometer.
7. One cannula will be inserted in the cubital vein for collection of blood samples. The
forearm from which blood samples are drawn will be wrapped in a heating blanket (42°C)
throughout the experiment (for arterialisation of venous blood).
8. Blood samples (for analysis of total amino acids, gut hormones, glucose, glucagon,
insulin, C-peptide, urea, FFA) will be measured throughout the OGTT (see Table 1).
9. At time 0 min, the participant will ingest 75 g of water-free glucose dissolved in 300
ml water over a period of 5 minutes.
10. At time 0, 30, 60, 90, 120, 150, 180, 210, 240 and after the ad libitum meal, hunger,
satiety, fullness and prospective food consumption will be measured by VASs
11. During the last hour (time 180 min - 240 min), REE will be measured in a supine position
by indirect calorimetry to determine oxygen consumption (V02) and carbon dioxide
production (VC02). A flow-through canopy gas analyser will be used, as previously
described.
12. At time 240 min, the subject will be asked to provide a new urine sample for measurement
of urea concentration. The participant will be asked to empty the urinary bladder
completely. Urine volume will be measured.
13. At time ~250 min, the participant will ingest a standardised ad libitum meal consisting
of minced meat, pasta, corn, carrots, peppers, cream, salt and pepper (50 energy (E)%
carbohydrate, 37 E% fat, 13 E% protein). The participant will be instructed to eat as
much as possible until feeling comfortable saturate. The meal should be consumed within
a maximum of 30 minutes and by the end of the meal, time spent eating, weight of the
meal and the total amount of energy consumed will be noted.
14. A continuous glucose monitor will be applied on the upper arm of the participant. The
sensor is blinded which means that the participant cannot see his blood glucose
excursions during the 14 days period of measurements.
At the end of the randomisation visit, the participant will be randomly assigned to one of
three interventions (1:1:1):
1. Two tablets of curcumin (corresponding to 200 mg) twice daily from day 1 to day 11 and
prednisolone capsule 50 mg (oral) once daily from day 2 to day 11
2. Two tablets of placebo-curcumin twice daily from day 1 to day 11 and prednisolone
capsule 50 mg once daily from day 2 to day 11, or
3. Two tablets of placebo-curcumin twice daily from day 1 to day 11 and
placebo-prednisolone capsule once daily from day 2 to day 11 The tablets with curcumin
and placebo-curcumin will appear identical, and the capsules with prednisolone or
placebo-prednisolone will appear identical.
The supplier of curcumin will also produce placebo-curcumin tablets (Indena Aps, Milan,
Italy). The pharmacy of Region H will be responsible of production and delivery of
prednisolone and placebo-prednisolon. Unblinded site-staff will be responsible for labelling
and blinding of the curcumin and placebo-curcumin tablets and prednisolone and
placebo-prednisolone capsules before the beginning of the intervention period. A person not
otherwise involved in the study will generate a randomisation code using a random list
generator. A randomisation list with randomisation numbers and corresponding treatment will
be made by the unblinded site-staff. A list with randomisation number and corresponding
packages with numbers will be made by unblinded site-staff, so that blinded site staff is
only allocating a randomisation number at the day of randomisation. The list with the
information about randomisation number and corresponding treatment will be kept at Center for
Clinical Metabolic Research at Gentofte Hospital. If a participant develops adverse events
(AEs) that demand knowledge of the content of the intervention, the list will show if the
patient is having any active ingredients. If a participant is excluded of the trial before
end-of-intervention visit, a new subject will be included in the same treatment-arm by taking
over the randomisation number.
The interventional period If the participant was tested for Sars-Cov2-infection at
randomization visit, this test has to be negative before start of intervention. If the
participant is included during COVID19 pandemic, a telephone call is made the day before
intervention start, to ensure the following guidelines are followed: If the participant has
experiences symptoms of COVID19 during the last seven days prior to intervention start or had
close contact with COVID19-patients, intervention will not be started.
Intervention will start soon after baseline MRS and randomisation visit. During the
intervention period, each participant will fill out a dairy to keep track of any new
concomitant medication, compliance and possible AEs. The participant will be asked to keep
the alcohol and smoking habits they might have had before screening and, thus, not to consume
more than 21 units of alcohol per week. Furthermore, they will be asked to consume no more
than 5 units in one night. The participant will be requested to maintain the level of
physical activity from before intervention during the interventional period. The participant
will be informed that if he feels more hungry than usual, he is allowed to eat extra. At day
5, 6 or 7 in the intervention period, the participant will receive a telephone call from the
investigator or other delegated site staff, checking on AEs, concomitant medication and
compliance, and to answer any questions from the participant. Furthermore, participants are
instructed to contact investigator or other delegated site staff in case of any questions or
intolerable side effects.
The tablets and capsules are preferably ingested with a meal and a small glass of water.
Should the participant forget to take a dose of curcumin/placebo curcumin, it can be ingested
until 6 hours before the next planned dose. If a dosage is missed, and the next one is
planned within 6 hours, the dosage should be passed, and the incident must be noted in the
diary. Should the participant forget to take a dose of prednisolone/placebo-prednisolone, it
can be ingested until 12 hours prior to the next dose. If a dosage is missed, and the next
one is planned within the next 12 hours, the dosage should med passed, and the incident must
be noted in the diary.
If the participant is included during COVID19 pandemic: The participant is instructed to
adhere to social distancing and to be aware of COVID19-symptoms, and call site staff in any
case of symptoms during intervention period or if he has had close contact to a person who
had a positive Sars-Cov2-test, and to immediately stop intake of intervention and
self-isolate in this case.
End-of-intervention assessments and visit The end-of-intervention visit will be planned on
day 12 after start of intervention. If the participant is included during COVID19 pandemic, a
telephone call is done the day before the visit to ask about recent symptoms of COVID19,
recent contacts to people with COVID19 symptoms or people with positive test for COVID19.
Stool sample collection and MRS will be performed in the period around end-of-intervention
visit, and will be performed as described above under "baseline assessments and randomisation
visit". Procedures during the end-of-intervention visit are similar to the ones described
above under "Baseline assessments and randomisation visit". Also, during this day, to check
for any effect of curcumin intervention, physical examination will be performed by a
physician from the research team and additional blood samples (identical with the samples at
the screening visit, except viral hepatitis markers) will be collected (which adds another 5
ml blood samples compared to randomisation visit) and albumin-creatinine ratio in the urine
will be measured. The continuous glucose monitor sensor is removed from the upper arm of the
participant, and the data from the sensor is transferred to a suitable software program.
Again, the questionnaire is handed out regarding calorie intake and physical activity the day
prior to the End-of-intervention day. Compliance will be evaluated (if compliance is
insufficient (missed more than ¼ of planned doses), the participant will not go through
end-of-intervention assessments). If the participant is included during COVID19 pandemic, he
is instructed to continue social distancing for three days after end-of-intervention visit.
Follow-up phone call and visit Between two and four days after last day on treatment, the
participant will receive a telephone call, where the participant is asked about withdrawal
symptoms and symptoms of COVID19. Due to COVID19, an extra telephone call is made at day 5-8
after end-of-intervention visit.
If the participant feels any kind of withdrawal symptoms (tiredness, weakness, abdominal
pain, anorexia, nausea or vomiting), or has had any symptoms of an ongoing infection after
End-of-intervention, a plan of action is made. Judged from the physical examination, blood
tests, results from continuous glucose monitoring, MRS and FibroScan at End-of-intervention
visit, a follow-up visit will be arranged, if it - judged by the investigator - is necessary.
At this follow-up visit (3-4 weeks after End-of-intervention) the investigator can do any or
all of the following tests; physical examination, FibroScan, measurement of IOC, standard
OGTT and blood tests, whichever is judged to be necessary to look into any late effects of
the intervention, and if necessary, another follow-up visit after another 1-3 months. If the
participant had steatosis on both MRS's, the participant will be offered a referral to the
Department of Gastroenterology for further evaluation and treatment.
BIOBANK A research biobank will be established at at Center for Clinical Metabolic Research
at Gentofte Hospital, DK-2900 Hellerup, Denmark, during the experiments to store the blood
tests until analyses. All participants are assigned with a trial number and will on data
sheets and tubes only appear with the trial number. The full name, social security number and
trial number will be stored separately. After the project is completed the biobank will be
terminated. Excess plasma will be stored in another biobank for up to 10 years after the
completion of the study, in case of need of re-analyses or need for further analyses. In the
latter case, a new approval by the Regional Health Research Ethics Committee is required. The
biobanks will be registered with Datatilsynet.
CALCULATIONS AND STATISTICS Data will be processed and presented with the use of standard
descriptive statistics. Areas under the curves (AUCs) are calculated by use of the trapezoid
rule. Comparison of normally distributed data is carried out by means of repeated
measurements analysis of variance using linear mixed modeling with "individual" as random
factor. Freidmans test will be used for analysis of non-normally distributed data. P values
≤0.05 are accepted as statistically significant (significance level, α = 5%). Power of the
study (1-β) is set to 80%, where β (20%) is the risk of accepting a hypothesis that is false.
Power calculation: Hansen et al. studied a prednisolone-treated group of healthy individuals,
and found an increase in HOMA-IR of 1.6 (1.3±0.1 vs. 2.9±0.3). The difference is 1.6±SD, but
the value of this SD we unfortunately do not have. Best guess is that it is (maximum) 0.5. It
is hypothesized that the intervention group receiving two different kinds of placebo is
comparable to the baseline values in KB Hansens study, both before and after intervention, as
placebo expectedly will not change HOMA-IR. And it is hypothesized that the prednisolone
treated group is comparable with KB Hansens cohort after treatment with prednisolone. The
wish is to achieve a reduction in the increase in HOMA-IR of 50% when ingesting curcumin,
which gives a minimal relevant difference of 0.8.
P values ≤ 0.05 are accepted as statistically significant (α = 5%) and the power is set to
80%. This results in a sample size of 7 in each of the three treatment groups. . Based on
this, we will include 9 in each of the three treatment groups, as we might have slightly more
variance in HOMA-IR in our population compared to KH Hansen's participants. In case of
drop-outs, we will include new participants until we have 12 completers in each group.
The continuous glucose monitoring will provide data for up to 14 days with glucose measures
with frequent intervals 24 hours per day. The CGM will be recording for at least 24 hours
before start of intervention with prednisolon. CGM recordings are regarded successful if at
least 80% of the sensor data are available for analysis. Before analysis, all data will be
reviewed for pressure induced sensor attenuations. From these data, the following
calculations will be made: 1) The risk of hypoglycemia and hyperglycemia will be calculated
as the low blood glucose index (LBGI) and the high blood glucose index (HBGI) using the
EasyGV workbook (www.phc.ox.ac.uk/research/technology-outputs/easygv) 2) coefficient of
variability (SD/mean interstitial glucose level), 3) SD, 4) percentage of time in
normoglycemic range (3,9-7,8 mmol/l), 5) percentage of time in three hyperglycemic ranges
(7.9-10 mmol/l, 10.1-13.9 mmol/l, >13.9mmol/l) and 6) percentage of time in hypoglycemia
(<3.9 mmol/l).
SIDE EFFECTS, RISKS AND DISADVANTAGES FOR PARTICIPANTS Curcumin is a polyphenolic compound
extracted from the turmeric root with a very low bioavailability. High doses of Meriva® have
been well tolerated in human trials. However, most studies have been performed with
non-formulated traditional curcumin with lower bioavailability. Nevertheless, high doses of
non-formulated curcumin have not been associated with severe side effects, and are generally
very well tolerated in clinical trials. Panahi et al did a study with NAFLD patients, with
~50 patients receiving Meriva® 1000 mg daily for 8 weeks (corresponding to 200 mg of
curcumin). There were no reports of side effects, but 7 withdraw because of the perception of
lack of effects. Antiga et. al. did a study with Meriva® 2000 mg daily for 12 weeks, with
only one participant having one adverse event (diarrhoea), but presumably not caused by
Meriva® because of other signs of viral genesis67. Mazzolani did a study with 12 patients
receiving 1200 mg Meriva® per day for 1 year with no reports of AEs. Di Pierro et al. did a
study on overweight participants, with a high dose of phosphatidylserine (a product very
similar to Meriva®) with reports of no side effects.
Prednisolone side effects are very well described, and most commonly are weight gain, skin
abnormalities, increased serum glucose levels, insulin resistance, oedema, electrolyte
derangement, myopathy, osteoporosis, infections, reduced symptoms of infections,
haematological abnormalities, psychiatric diseases, mood changes, sleep disorders,
hyperlipidaemia, hypertension and heart failure. But if the participants will experience side
effects, they are unlikely to get severe, when treating only with 50 mg daily for 10 days, as
they are dose and time-dependent, and with the relevant inclusion and exclusion criteria
applied. Furthermore, they are all regarded as fully reversible after end of intervention.
A side effect from treatment with oral corticosteroids (e.g. Prednisolone) is elevated IOP
which in rare cases can cause the sight-threatening condition, glaucoma. In most cases
elevated IOP is asymptomatic, which is why, it is important to measure in the patient. IOP
can simply and easily be measured with a icare ic100 tonometer. The device is based on a
rebound measuring principle that requires no drops, air or specialized skills for its use,
and therefore not associated with any risk or complications. IOP is measured 3 times in each
eye and the mean is calculated. If this is elevated the patient will be seen by an
ophthalmologist.
During and right after prednisolone treatment, the participants are more prone to infections
and are likely to have fewer symptoms of infections. Participants will be asked about their
wellbeing and symptoms of infection several times during the trial.
If the participant is included during the COVID19 pandemic, several extra restrictions and
assessments are applied in the study, due to the possible increased risk of a severe course
of COVID19 in case of prednisolone treatment. This is applied only to take extraordinary
precautions. Information on these restrictions and assessments is found in the relevant parts
of this protocol. Participants are thoroughly instructed in the relevant changes in the
participant information documents before screening.
Withdrawal symptoms (after prednisolone treatment) are most commonly tiredness, weakness,
abdominal pain, anorexia, nausea or vomiting. Due to the short treatment period and
relatively low dose, it is very unlikely these symptoms will occur, but participants will be
asked about these symptoms at the telephone call two to four days after last day on
treatment.
MRS is safe and not coupled with discomfort or pain. The scanner will be making loud noise
while scanning, but the participant will wear proper ear protection. Some participants may
experience claustrophobia during the scan. If the participant has steatosis on both MRS, he
will be offered a referral to the Department of Gastroenterology.
Penetrations of skin (blood puncture and intravenous catheter insertion and insertion of
sensor for continuous glucose monitoring) are associated with mild discomfort and risk of
hematomas. A theoretical complication to skin penetration is superficial phlebitis. The
condition is not dangerous and will be treated with antibiotics should any sign of infection
be present. The risk of superficial phlebitis is small and minimized by following clinical
standards for the insertion of intravascular catheters including double wiping of the
involved skin with disinfectant alcohol and other sterile procedures.
The total blood loss will amount to approximately 365 ml distributed over a minimum of 2
weeks, which is not in any way harmful for the participant. Only participants with
haemoglobin >7.5 mmol/l can participate, and all participants are offered iron treatment
after the trial.
PARTICIPANTS PHYSICAL AND MENTAL INTEGRITY AND PRIVACY Information regarding participants of
the project will be protected in accordance with the applicable laws of Denmark including the
law concerning the processing of personal data. We will seek approval of the protocol by the
Danish "Datatilsynet" via the The Capital Region of Denmark. The trial will follow the rules
in European Union's General Data Protection Regulation.
The protocol complies with the Helsinki Declaration (Seventh revision 2013).
OPERATING COSTS AND ECONOMY The project is currently not supported by any medical companies
and the responsible physician of the project has no economical affiliations with private
companies, foundations or the like with interests in the research project. When funding for
the project is in place the Research Ethics Committees will be notified.
AVAILABILITY OF DATA FOR PARTICIPANTS All participants are guaranteed access to more
information about the project. Contact: Dr. Pernille Høgh Hellmann, MD, Center for Clinical
Metabolic Research, Gentofte Hospital, DK-2900 Hellerup; e-mail:
pernille.hoegh.hellmann@regionh.dk; Phone: +45 20911792.
ADJOURNMENT OF TRIAL Any participant can be withdrawn from the trial at any time, in case
investigator finds it unsafe for the participant to continue. Also, the participant can be
withdrawn if the participant meets any of the exclusion criteria, if compliance is
insufficient (if participant has missed more than ¼ of planned doses, controlled at telephone
call at day 5, 6 or 7 in the intervention period and at the end-of-intervention visit)
evaluated by investigator, or in case exceptional circumstances make it impossible to
complete the study. Likewise, any extraordinary event that makes it impossible to finish the
project will result in termination of ongoing experiments. In all cases, the participant will
be informed about the decision and the reason why. The participant may, at any time during
the trial, voluntarily discontinue participation. In case of drop-outs, we will include new
participants until we have 12 completers in each group.
THE RESEARCH GROUP Pernille Høgh Hellmann MD, Jonatan Ising Bagger PhD MD, Katrine Bagge
Hansen PhD MD, Professor Tina Vilsbøll DMSc MD, Professor Filip Krag Knop PhD, MD
RECRUITMENT OF PARTICIPANTS Participants are recruited through the following methods: 1)
Advertisement in newspapers or local newspapers or at www.forsøgsperson.dk. 2) Advertisement
through flyers and posters. 3) Participants who participated in studies in the department in
the past and gave consent that they would like to be contacted again in regard to
participation in new studies in the department.
Participants who responded on advertisements will receive written information on e-mail or
regular mail, whatever is preferred. All participants will also receive the leaflet
"Forsøgspersonens rettigheder i et sundhedsvidenskabeligt forskningsprojekt" from the Ethical
Committee in Denmark, august 2014.
After at least two days, the participant will be contacted by telephone and asked if he wants
to participate in the study. If the participant has any questions, these will be answered as
thoroughly as possible. If the participant is interested in participation, a time and place
for the information visit will be scheduled. During the phone call, the participant is
informed about the possibility to be accompanied by a person of own choice to all the visits
during the trial.
