Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05231642 |
| Other study ID # |
IRAS308018 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 30, 2021 |
| Est. completion date |
December 20, 2022 |
Study information
| Verified date |
October 2023 |
| Source |
University of Sunderland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Type 1 diabetes (T1D) is a lifelong disease which stops the body from producing insulin - an
important hormone that controls blood sugar (glucose) levels. People with T1D use insulin
replacement therapy, usually in the form of injections, to help control blood glucose levels,
however keeping glucose levels within normal ranges is usually a challenge. Mealtime glucose
control is fundamental to good diabetes management and are an important contributor to
long-term diabetes complications. However, many individuals experience variability in glucose
levels around mealtimes. The objective of this study is to establish whether and which
parameters are important predictors of mealtime glucose levels in people with T1D.
The investigators will monitor glucose levels using the latest glucose monitoring technology
and collect blood samples to:
1. Characterise changes in glucose levels in individuals with T1D in response to different
meals
2. Determine whether and what food characteristics and personal factors are linked to
individual glucose responses to different meals.
The investigators will recruit 150 individuals with type 1 diabetes. Firstly participants
will attend a preliminary visit, where a blood sample will be donated to study laboratory
blood markers of vascular and metabolic health accompanied by a full medical examination in
which body composition will be established. During this visit participants will also complete
questionnaires about their lifestyle, and be fitted with two wearable devices to monitor
glucose levels and physical activity levels under free-living conditions.
After 4-weeks of wearing the devices, participants will attend two experimental laboratory
visits where breakfast and lunch will be served and blood samples taken. This will enable us
to observe glucose and metabolic responses to feeding under controlled conditions.
Description:
Recruitment: Participants will be recruited using advertisements through university channels.
The investigators will also approach local and national diabetes charities (Diabetes UK,
JDRF) who the investigators work with closely to advertise through written publications
(patient magazines), websites, social media, and patient support groups. In addition, the
investigators will contact patients who have previously participated in our research who have
consented to being contacted about future research. Contact information for the research team
will be provided in advertisements; an initial telephone call will be available to interested
participants to discuss the study, answer any questions, and obtain contact information to
send a study information pack including a participant information sheet. Participants will be
given 6-weeks to decide whether to participate in the study.
Preliminary visit: Patients will attend a preliminary visit to our dedicated laboratories at
the University of Sunderland to assess eligibility and obtain written informed consent by a
GCP trained member of the research team. At this visit, consented participants will be fitted
with a blinded real-time CGM and an accelerometer and provided with a food diary. During this
visit, patients will complete a questionnaire to assess their medical history and physical
activity. Both CGM and accelerometer devices will be worn by participants for the duration of
their study involvement; both devices complete with data capture will be returned by
participants to the research team either in person or via post (using a prepaid envelope).
CGM measurement: A small CGM device (CGM; Freestyle Libre Pro; Abbott Diabetes Care) will be
inserted during the preliminary visit to the laboratory. It is a small discreet,
water-resistant sensor, with a thin filament (<0.4m thick) that is inserted (painlessly) 5mm
beneath the skin surface on the upper arm. The sensor will be inserted into the subcutaneous
tissue on the anterior of the upper arm. The insertion site will be taken as equidistant
between the most medial portion of the upper arm and marked with indelible ink so that
initial placement can be replicated on subsequent insertions in the unlikely event that a
sensor should fail. The sensor is factory calibrated making it far more convenient and
removing the risk for sensor inaccuracies from calibration user error (capillary meter
inaccuracy, not washing hands etc) seen with other CGM devices. Glucose data generated by the
CGM is masked (i.e., participants cannot see their glucose data and thus cannot change their
treatment regimen based on this information). A single reader device is used to activate and
retrieve the data. The accuracy and safety of this device has been established in T1D across
the full range of glucose levels likely to be observed in this study, including those in the
normal range; the latest generation of the CGM sensor has a MARD of <9% as of 2018. Moreover,
as an un-blinded version of this device is now made available to people with T1D with
treatment indications through the NHS, the use of this technology is deemed acceptable to
people with T1D. Study participants who are using Freestyle Libre to monitor their glucose
patterns can continue to use the device as usual but will be asked to wear an additional
blinded sensor. In total, patients will be requested to wear the CGM device for 6 continuous
weeks, consisting of 4-weeks observation followed by 2-weeks observation during which
laboratory experimental testing will occur.
Accelerometer: Participants will be issued and fitted with an accelerometer (GeneActiv, worn
on the arm) which will provide a comprehensive assessment of sitting/standing patterns (i.e.
posture allocated) and physical activity levels. The data collected from this device will be
used to estimate daily energy expenditure (using a priori cut points) and calculate physical
activity levels including time spent in different postures and activities during discrete
parts of the day both before and after each laboratory visit. This will allow for
quantification, standardisation and replication of physical activity patterns during
free-living episodes. In total, patients will be requested to wear the accelerometer device
for 2 continuous weeks.
Medical history: To include: age, gender, duration of diabetes, insulin therapy (average
total daily dose and basal insulin dose), associated medical conditions, family history of
T2D and cardiovascular disease, hypoglycaemia unawareness (assessed through a combination of
the Clarke and Gold methods).
Physical activity assessment: Patients will complete the IPAQ (International Physical
Activity Questionnaire), the Exercise Benefits/Barriers Scale Questionnaire, and The Barriers
to Physical Activity in Type 1 Diabetes Scale. These will assess current levels of physical
activity participation, as well as general and diabetes-specific enablers and barriers to
physical activity.
Anthropometrics: Anthropometric data will include: weight, height, waist circumference and
waist-hip-ratio. Body composition will be determined using the bioelectrical impedance method
[Seca mBCA 525] as detailed above. Blood pressure will be taken alongside ankle brachial
index measurements. Estimated glucose disposal rate (eGDR; a measure of insulin resistance)
will be calculated for all patients.
Dietary assessment: Patients will complete a food frequency questionnaire (Dietary Instrument
for Nutrition Education) and will be provided with a food scale and a food diary to perform a
weighed food log. In total, participants will complete the weighed food diary for 1-week.
Blood donation: A single 50mL blood donation will be made which will be retrospectively
analysed for parameters of vascular and metabolic health. Blood will be obtained using
venepuncture technique by a trained phlebotomist.
Experimental laboratory visits Pre-laboratory phase: Prior to the first experimental visit,
the investigators will assess glycaemic control (CGM) and physical activity patterns
(accelerometer) for 4- and 1-weeks, respectively. Patients will be required to use their
dietary recording sheets to replicate their dietary patterns in the 48-hours prior to each
experimental laboratory visit. For standardisation of glycaemic control, as well as
biochemical parameters, participants will be provided with a standardised meal to be consumed
on the evening before each experimental laboratory visit based upon their weight (~635kcal;
vegetarian lasagne; Tesco). Since an acute exercise session may enhance insulin action for up
to 48-hours, participants will be asked to reframe from moderate-to-vigorous physical
activity/exercise during the 48-hours preceding each laboratory visit to avoid the potential
impact of this on glycaemia and hypoglycaemia risk. Additionally, during the 24-hour prior to
each laboratory visit, participants will be asked to reframe from caffeine and alcohol which
are known to influence glucose levels.
To avoid any confounding influence of hyper/hypoglycaemia or illness, a researcher will call
the morning of each testing day - if blood glucose is outside the range of 4-12 mmol/L or if
the participant is unwell with blood ketones >0.6 mmol/L, the experimental visit will be
postponed. The dosage and timing of insulin administrations as well as any
supplements/vitamins being taken will be standardised for the duration of each trial period.
To control for the potential confounding effect of insulin regimen (CSII vs MDI) and
medication, insulin regimen and medication will be included as a covariate in the statistical
model. Participants using CSII will be advised to avoid making changes to their insulin pump
delivery settings and insulin regimen between study visits. Participants treated with MDI
will be advised not to change their insulin regimen between study visits. Due to the
likelihood of changes in glycaemic control and/or insulin requirements over longer periods of
time, pre-menopausal women will complete each condition with a 1-week washout, as for all
other participants. Menstrual phase will be recorded for each condition and controlled for as
a covariate in statistical models.
Main experimental visits: In a randomised crossover design, patients will attend two separate
morning-time (~08:00am) laboratory-based visits (lasting ~4.5-hours in duration) within the
dedicated clinical testing facility at the Univeristy of Sunderland, each interspersed by one
week. Each experimental condition will be conducted in a controlled laboratory setting to
maximise internal validity and minimise the inherent variability of less-controlled
'real-world' settings. Except for toilet breaks, participants will be seated in a comfortable
lounge-chair and instructed to minimise excessive movement.
On each occasion and upon arrival to the laboratory following an overnight fast, participants
will assume a seated and rested position while a 20-gauge cannula (Vasofix, B. Braun,
Melsungen AG, Melsungen, Germany) is inserted into the antecubital vein of their non-dominant
arm; resting, fasted venous blood samples will be collected prior to experimental testing.
Following the initial blood sample, patients will be given a standardised mixed-macronutrient
breakfast-based meal on each occasion. At 4-hours post-breakfast, participants will be
provided with a standardised mixed-macronutrient lunch meal before being discharged home.
Each meal will be matched for carbohydrate (equating 1g.carbohydrate.kg.BM-1 ), fat, protein,
and fibre content but differing in glycaemic index through manipulation of carbohydrate
composition to represent either a low or high glycaemic index meal. Insulin administration
will be standardised across visits based on the carbohydrate counting method. Meals will be
preceded by an insulin bolus, calculated from each participant's usual
insulin-to-carbohydrate ratio (with no correction dose), administered 10-minutes before
eating, with those treated on MDI standardising insulin injection site. The timing and amount
of water consumed with each meal, and ad libitum throughout the duration of the first visit
will be recorded so that this can be replicated on subsequent visits.
Blood sampling: Periodic blood samples will be drawn at 30-minute intervals across the 4-hour
observation window and commencing immediately prior to the consumption of the breakfast
meal). At each time point, 10mL of venous whole blood will be taken and dispensed into
Vacutainers before centrifugation at 3000 rev/min for 15-minutes at 4ºC. Plasma will be
separated and stored at -80 degrees centigrade for retrospective analysis, or immediate
analysis for a panel of vascular inflammatory and thrombotic parameters, including plasma
levels of C-reactive protein (CRP), complement C3, fibrinogen, plasminogen activator
inhibitors (PAI)-1, interleukin 1b, will be assessed using standard ELISA techniques. An
additional 5mL of venous blood will be taken at rest on one arm of the study for C-peptide
and routine blood tests (including HbA1c, U&Es, LFTs, full lipid profile, urinary albumin
creatinine ratio (unless these have been done within three months of enrolment). A total of 8
blood samples will be taken with the total volume of blood equalling 85mL, which is
approximately 1/5th of a full blood donation. The total volume of blood to be taken is safe
and is similar to other studies that the investigators have performed previously in people
with T1D. Further, the investigators have worked hard with our PPI representatives to
minimise the participant burden of all study procedures; the volume and frequency of blood
sampling has been deemed acceptable by our PPI representatives.
Post-laboratory observation period:
Following the last blood sample at 7-hours post-breakfast, participants will be discharged
from the laboratory. Glycaemia will continue to be monitored under free-living conditions for
a total of 48-hours post-intervention using CGM. As the investigators are interested in the
48-hour glucose responses following our intervention (including the dawn phenomenon),
participants will be given two standardised meals to consume as their evening meal and
breakfast and be required to replicate their dietary intake across trials for the duration of
the 48-hour post-intervention period, in order to control for the potentially confounding
effects of diet on glycaemic control.
