Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05762120 |
| Other study ID # |
2022/00652 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 3, 2023 |
| Est. completion date |
March 2025 |
Study information
| Verified date |
March 2023 |
| Source |
National Healthcare Group Polyclinics |
| Contact |
Wern Ee Tang |
| Phone |
(65) 63553000 |
| Email |
wern_ee_tang[@]nhgp.com.sg |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to determine the effectiveness of a weight management
programme in primary care in achieving diabetes remission in obese patients with early
diabetes.
Potential participants are to attend a screening visit to determine eligibility. Eligible
participants will be invited to participate in the trial within 3 months of screening visit.
120 participants will be recruited into the study and randomised into 2 arms: control group
(60 participants) or intervention group (60 participants).
Control group: Participants randomised to the control group will receive usual care with
their healthcare team.
Intervention group: Participants randomised to the intervention group will be put on a weight
management programme with the aim of achieving weight loss of at least 15% body weight or
15kg.
Researchers will compare between control and intervention groups to see if a weight
management programme is effective in achieving diabetes remission in obese patients with
early diabetes, compared to usual care.
Description:
CONTROL GROUP
Participants randomised to the control group will receive usual care that does not include
very low calorie diet (VLCD). They will be offered up to 6 dietitian consultations and 6
nurse diabetes counselling sessions (optional) over 18 months (78 weeks). They will be
provided a wearable device to monitor their physical activity.
INTERVENTION GROUP
Phase A - Very low calorie diet (VLCD) phase (800kcal/day) (12 weeks)
- A commercially available micronutrient-replete 840kj/201kcal liquid formula diet
(shakes) will be provided (Optifast, Nestle Health Science) to replace usual foods, with
ample fluids for 12 weeks.
- Soluble fibre supplements (Fybogel 2 x 3.5 g/day) will be provided to participants to
reduce constipation.
- Oral hypoglycaemic agents will be withdrawn at the start of this phase. Oral
hypoglycaemic agents may be reintroduced if blood glucose levels are found to be
persistently elevated.
- Participants who are on antihypertensive medications will have their antihypertensive
medications withdrawn. Blood pressure will be closely monitored in these participants
and antihypertensives reintroduced if blood pressure levels are found to be persistently
elevated.
- During this phase, continuous glucose monitoring will be carried out for the first 2
weeks.
- After the first 2 weeks of this phase, participants are encouraged to monitor their
glucose levels (fasting or random) using a glucometer 2 times a week.
- If they achieve BMI below 21kg/m2 or 15% body weight loss or 15kg weight loss before 12
weeks, they will be moved into the LCD phase.
- During the VLCD phase, participants will be encouraged to maintain their usual physical
activities, but not increase physical activity.
- Each participant will be provided a wearable device to monitor their physical activity
levels.
Phase B - Low calorie diet (LCD) phase (1,000-1,200kcal/day) (12-14 weeks)
- Participants will transit from meal replacement in the VLCD phase to taking in normal
food.
- During this phase, continuous glucose monitoring will be carried out for the first 2
weeks.
- After the first 2 weeks of this phase, participants are encouraged to monitor their
glucose levels (fasting or random) using a glucometer 2 times a week.
- During this phase, participants will be reviewed at 4 to 6-weekly intervals.
- During the first 4 weeks of this phase, participants will be encouraged to maintain
their usual physical activities but not increase physical activity.
- After 4 weeks in this phase, incremental physical activities will be introduced to
participants who are physically able, with the aim of achieving 7,500-10,000 steps per
day.
- Physical activity will be monitored using a wearable device.
- If the participants' BMI falls below 21kg/m2, or lose 15%, or 15kg of their body weight,
they will be moved into the maintenance phase.
Phase C - Maintenance phase (1,200-1,500kcal/day) (24-26 weeks)
- Participants will be advised to maintain on a 1,200-1,500kcal/day food-based diet plan
to support weight stabilisation and prevent weight regain.
- Participants to complete 3 day food diary before each dietitian visit.
- Continuous glucose monitoring will be carried out for the first 2 weeks of the
maintenance phase.
- After the first 2 weeks of this phase, participants are encouraged to monitor their
glucose levels (fasting or random) using a glucometer 2 times a week.
- Participants who are physically able will be encouraged to have regular physical
activity up to a maximum of 15,000 steps per day.
- During the maintenance phase, participants will be reviewed regularly at approximately
12 to 16 weekly intervals.
Phase D - Continuance phase (24-26 weeks)
- During the continuance phase, participants will be advised to adhere to a healthy,
balanced diet
- Participants to complete 3 day food diary before each dietitian visit.
- Continuous glucose monitoring will be carried out during the first 2 weeks of the
continuance phase.
- After the first 2 weeks of this phase, participants are encouraged to monitor their
glucose levels (fasting or random) using a glucometer 2 times a week.
- Physical activity will be monitored using a wearable device.
- Participants will be reviewed regularly at approximately 12 to 16 weekly intervals for
monitoring.
METHODS AND ASSESSMENTS
- Height will be measured to the nearest mm, with the Frankfort plane horizontal, using a
stadiometer.
- Body weight will be measured to the nearest 100 g in light clothing without shoes using
Class 111 approved calibrated scale.
- Waist circumference will be measured halfway between the point of the lowest rib and the
iliac crest.
- Hip circumference will be measured at the maximum circumference around the buttocks.
- Blood pressure will be measured with patients seated, at rest, with legs uncrossed for
at least 5 minutes.
- Blood will be collected to measure electrolytes, liver function tests (ALT and AST),
lipid panel, HbA1c, creatinine, fasting glucose (venous), glucose (capillary),
C-peptide, urine microalbumin and full blood count.
- Physical activity will be assessed at week 12, 16, 26, 38, 52, 64 and 78 in the
intervention group and at week 12, 26, 38, 52, 64 and 78 in the control group using a
wearable tracker for activity and sleep tracking. The device is to be worn by
participants for approximately 9 days before each data collection time point.
- Questionnaires including health-related quality of life, diabetes empowerment scale and
diabetes distress scale, fat and fibre questionnaire, dietary questionnaire and physical
activity questionnaire will be administered at baseline, week 26, 52 and 78 for all
participants.
CONTRACEPTION AND PREGNANCY TESTING
Urine pregnancy test is performed at screening visit for women with reproductive capacity
(pre-menopause without hysterectomy) to exclude pregnancy. Those who are considering
pregnancy during the study period will be excluded. Women with reproductive capacity will be
advised not to plan for pregnancy during the study period. Urine pregnancy test will be done
at baseline, 6, 12 and 18 months (week 0, 26, 52 and 78) for all female participants with
reproductive capacity. Participants who have a positive urine pregnancy test will be dropped
from the study.
RELAPSE MANAGEMENT FOR WEIGHT REGAIN
If weight regain occurs, or if diabetes is found to have returned (HbA1c ≥6.5%) at any time
during the first 52 week period, 'rescue plans' to reverse weight gain will be offered.
1. Weight regain of >2 kg: offer LCD using meal replacement to replace one or two main-meal
per day for 4 weeks.
2. Weight gain of >4 kg, or to <15 kg below starting weight or if diabetes recurs: offer 4
weeks VLCD using meal replacement with fortnightly dietitian review and then a 2-4 weeks
LCD. Individualised dietary advice and physical activity targets will be reinforced for
weight loss maintenance.
EXPECTED RISKS
Expected risks to the subjects in the intervention arm are:
- when in the very low calorie diet phase of the study are symptoms of ketosis (such as
feeling thirstier than usual, muscle cramps, headaches, fatigue and weakness), feeling
hungry, constipation and diarrhoea.
- fluctuations in blood glucose and blood pressure
Patients will be monitored closely and medical attention given to patient when any of the
symptoms are detected.
AE REPORTING AND FOLLOW-UP
Subjects will be monitored for any adverse events at each study visit. Any adverse event will
be reported to the PI and followed up as appropriate.
SAE REPORTING
SAEs that are unanticipated, serious, and possibly related to the study intervention will be
reported to the Independent Monitor and DSRB in accordance with requirements.
- Unexpected fatal or life-threatening AEs related to the intervention will be reported to
the DSRB within 7 days. Other serious and unexpected AEs related to the intervention
will be reported to the DSRB within 15 days.
- Anticipated or unrelated SAEs will be handled in a less urgent manner but will be
reported to the Independent Monitor and NHG DSRB. In the annual AE summary, the
Independent Monitor Report will state that they have reviewed all AE reports.
SAFETY REVIEW PLAN
Study progress and safety will be reviewed quarterly (and more frequently if needed).
Progress reports, including patient recruitment, retention/attrition, and AEs, will be
provided to the Independent Monitor following each of the quarterly reviews.
DESIGNATION OF AN INDEPENDENT MONITOR
The Independent Monitor for this study has been appointed from National Healthcare Group
Polyclinics. The Independent Monitor is not a member of the study team and works
independently of the PI.
DATA QUALITY ASSURANCE
Description of Plan for Data Quality and Management
The PI or study team member will review all data collection forms on an ongoing basis for
data completeness and accuracy as well as protocol compliance.
Collected data will be verified by checking primary and secondary endpoint data against
original source documents. Data verification will be performed by someone other than the
individual who originally collected the data.
DATA ENTRY AND STORAGE
For hardcopy data, they will be stored in designated locked cabinet(s) or room(s) that are
accessible to authorized study personnel only. For electronic data, they will be stored on in
a secured computer that is password protected. The databases will not contain subject
identifiers and the data linking subject identifiers and the subject identification codes
will be stored separately.
SAMPLE SIZE AND STATISTICAL METHODS
Determination of Sample Size
120 participants (60 per arm) will be recruited to the study. Power calculation has assumed
diabetes remission in 27% of intervention participants at one year compared with 5% in the
control group. Recruitment of at least 42 participants per arm will provide over 80% power at
alpha = 0.05. Allowing for an estimated 30% individual participant drop-out within 12 months
(52 weeks), we will recruit a total of 120 participants (60 per arm).
Statistical and Analytical Plans
Primary outcome measures will be analysed in a hierarchical fashion, first analysing
reduction in weight of 15% body weight or 15 kg or more as a binary outcome with significance
assessed at the 5% significance level, followed, if the first test is significant, by test of
remission of diabetes status as a binary outcome also at the 5% level of significance.
Outcome data will be analysed initially on an intention-to-treat (ITT) basis at the 18 months
(78 weeks) time point. Participants reporting drug intolerance, diet intolerance or
poor-compliance will be recorded and these participants will be included in the ITT analysis.
For participants who discontinue the formal weight management programme the best available
follow-up weights and the end of study diabetes status will be used.
Descriptive analyses will be obtained for patients in both groups. Continuous variables will
be presented as mean (SD) or median (range) while categorical variables will be reported as
frequencies and percentages. Plots will be generated to highlight the distribution of
observations or trends. Based on the normality distribution of continuous data, the test for
significance will be performed using either independent t-test or Mann-Whitney U test as
appropriate. Dichotomous and categorical data will be performed using the Fisher's exact
test. A p-value of < 0.05 will be regarded as statistically significant. A secondary per
protocol 'completer's analyses' of those who complete the intended management will be
performed as well. Data will be analysed using Stata version 17.0 for Windows (StataCorp LLC,
College Station, TX).
