Obesity, Aging
Conditions
Keywords
Body composition, Adipose tissue, semaglutide
Brief summary
This is a single-center, prospective, controlled, randomized and open label study to investigate the effect of the semaglutide addition to standard of care weight loss intervention (personalized lifestyle and exercise) in elderly obese subjects on body weight and body composition as assessed by DEXA.
Detailed description
This will be a single center, prospective, open label, randomized and controlled pilot study to investigate the effects of semaglutide addition to a standard weight loss intervention program for 16 weeks on body weight and composition, adipose tissue metabolism and muscle strength compared to the standard weight loss program alone in elderly obese patients. Eligible and qualified patients will be randomized 1:1 in pairs (8 pairs) matched by age and BMI within 5% and by gender to one of two open-label interventions. Priority of enrollment will be to match already existing and non-matched pair(s) before starting new ones. However, participants will not need to wait until they are matched to be enrolled in the study. The two open-label interventions are: 1. Control group: Standard of care weight loss program that includes lifestyle changes and personalized exercise and dietary education. 2. Semaglutide group: semaglutide (up to 1mg) once weekly injection added to the standard of care weight loss program. Semaglutide dose will be started at 0.25 mg dose during the baseline visit and doubled every 2 weeks up to 1mg dose or up to maximum tolerable dose. Patients will be instructed on how to inject themselves with the drug and how to increase the dose. During dose escalation, we will be monitoring the subject more extensively (4 weeks and 8 weeks), compared to clinical practice, for any side effects including if they experience any GI side effects, and subjects will be kept at the maximum tolerable dose up to 1mg/week. At the baseline visit, and for all other visits, patients will come fasting (10 -12 hours) to the research center. Patients will visit the research center at 4 weeks (safety visit), 8 weeks and at 16 weeks (final study assessment visit). Blood (about 25 ml), body weight and other vitals, adverse events including hypoglycemia (blood sugar \<70 mg/dl) will be collected at all visits. Fat biopsy aspiration, DEXA scans, muscle strength measurement and age-appropriate quality of life questionnaire (Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) will be performed at 0- and 16-weeks visits. All patients will receive instructions at the beginning of the study on weight loss nutritional program and appropriate physical activity to be performed for the next 16 weeks. The program will be based, in-part, on dietary and exercise habits collected at screening visit. For the entire duration of the study, participants will maintain a daily diary to document food and exercise activities to ensure compliance with lifestyle program provided. At the 4- and 8-weeks visits, the daily diary will be reviewed for food and exercise activities, and instructions will be provided again to reinforce intervention. Patients will be provided with glucose meter and glucose strips to measure fingerpick blood glucose. For the entire duration of the study, patients will be asked to measure their blood sugars at least one time after exercise and to record any hypoglycemic events (glucose \<70mg/dl) in their diary, Patients will be instructed to record any other untoward side effects like nausea, vomiting, changes in appetite and other experiences in the diary. Patients will be instructed to call the Diabetes Center to speak to a study investigator directly in case of any problem or untoward side effects. they have a question or side effects. Standard of care weight loss program: All patients will be instructed to implement dietary and exercise program for the next 16 weeks and to record their activities on daily food and exercise diary provided. 1. Energy intake should be reduced by 500-750kcal/day. 2. Dietary fat should be reduced to 30% of total energy intake maximally. 3. Meal replacements (if used) will be consumed during breakfast and lunch. 4. Dinner consisted of conventional food and participants will be encouraged to eat fruits and vegetables within their calorie limit. 5. Participants should ingest 1.0-1.5g of protein/kg/day and spread consumption equally throughout the day. A leucine-enriched balanced amino acid supplement can be used. 6. Subjects will be instructed to perform aerobic, muscle-strengthening, flexibility, and balance exercises. Minimally, this should include moderate-intensity aerobic activity for 30 minutes five days per week or vigorous-intensity aerobic activity for 20 minutes three days a week, 10-15 repetitions of 8-10 major muscle group strengthening exercises two or more nonconsecutive days each week, 10 minutes of flexibility activities at least two days a week, and balance exercises three times a week for fall prevention.
Interventions
semaglutide (up to 1mg) once weekly injection added to the standard of care weight loss program. Semaglutide dose will be started at 0.25 mg dose during the baseline visit and doubled every 2 weeks up to 1mg dose or up to maximum tolerable dose for total of 16 weeks of intervention
Sponsors
National Center for Advancing Translational Sciences (NCATS)
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-center, prospective, controlled, randomized and open label study
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males and females age: ≥65 years 2. BMI ≥30 Kg/m2 AND waist circumference for women: \> 80 cm and for men: \> 90 cm 3. Stable body weight (no more than ±3 kg change during the 3 months prior to screening) 4. Able to participate in personalized physical activities and dietary instructions. 5. Participant must be able to read, write, and understand the English language and be able to provide written consent.
Exclusion criteria
1. Current diagnosis of weight changing condition including cancer, gastrointestinal conditions or eating disorders 2. GLP-1R agonists use within last 6 months 3. Diagnosis of type 1 or 2 diabetes 4. Impaired cognitive function (VA-St. Louis University Mental Survey (VA-SLUMS) score ≤ 19) 5. History of chronic/idiopathic acute pancreatitis 6. Personal/family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 7. Previous surgical treatment for obesity 8. Smoking or use of any nicotine products 9. Use of any medication that could interfere with trial results especially weight management drugs 10. Anticipated change in lifestyle (e.g., dietary, exercise or sleeping pattern) other than provided by the study. 11. Hepatic disease or cirrhosis 12. Aspartate Aminotransferase (AST) \> 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) \> 3X ULN 13. Inability to give informed consent 14. History of gastroparesis 15. History of serious hypersensitivity reaction to these agents 16. Alcoholism 17. Patients with retinopathy 18. Participation in any other concurrent interventional clinical trial -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio | 16 weeks | total fat mass/total fat-free mass ratio reported as arbitrary units (ratio), calculated by dividing total fat mass by total fat-free mass (lean mass) at baseline and at 16 weeks in both groups. Primary measurements of fat and fat-free mass is done using DEXA |
| Body Weight | 16 weeks | body weight reported in Kg at at baseline and at 16 weeks in both groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Fat Mass | 16 weeks | total fat mass reported in Kg and measured using DEXA at baseline and at 16 weeks in both groups |
| Total Fat-free Mass (Lean Mass) | 16 weeks | total fat-free mass (lean mass) reported in Kg and measured using DEXA at baseline and at 16 weeks in both groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide Semaglutide, added to standard of care, starting dose of 0.25mg titrated up to 1mg dose. for a total of 16 weeks.
Semaglutide Pen Injector: semaglutide (up to 1mg) once weekly injection added to the standard of care weight loss program. Semaglutide dose will be started at 0.25 mg dose during the baseline visit and doubled every 2 weeks up to 1mg dose or up to maximum tolerable dose for total of 16 weeks of intervention | 7 |
| Standard of Care Only Standard of Care (SOC) weight loss intervention alone (personalized lifestyle and exercise) | 7 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Standard of Care Only | Total | Semaglutide |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 5.1 | 69.8 years STANDARD_DEVIATION 4.9 | 70.0 years STANDARD_DEVIATION 5 |
| Body mass index (BMI) | 37.0 Kg/m^2 STANDARD_DEVIATION 4.3 | 37.8 Kg/m^2 STANDARD_DEVIATION 4.4 | 38.2 Kg/m^2 STANDARD_DEVIATION 4.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 14 Participants | 7 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
| Total Fat-Free Mass | 47.8 Kg STANDARD_DEVIATION 6.4 | 49.4 Kg STANDARD_DEVIATION 8.7 | 51.0 Kg STANDARD_DEVIATION 11.4 |
| Total Fat Mass | 47.8 Kg STANDARD_DEVIATION 9.3 | 50.0 Kg STANDARD_DEVIATION 9 | 52.1 Kg STANDARD_DEVIATION 8.9 |
| Weight | 100.0 Kg STANDARD_DEVIATION 17.8 | 103.9 Kg STANDARD_DEVIATION 19.5 | 107.8 Kg STANDARD_DEVIATION 19.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 5 / 7 | 1 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio
total fat mass/total fat-free mass ratio reported as arbitrary units (ratio), calculated by dividing total fat mass by total fat-free mass (lean mass) at baseline and at 16 weeks in both groups. Primary measurements of fat and fat-free mass is done using DEXA
Time frame: 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide | Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio | Baseline | 1.04 Arbitrary units (ratio) | Standard Error 0.07 |
| Semaglutide | Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio | 16 Weeks | 0.96 Arbitrary units (ratio) | Standard Error 0.06 |
| Standard of Care Only | Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio | 16 Weeks | 0.99 Arbitrary units (ratio) | Standard Error 0.07 |
| Standard of Care Only | Body Composition as Total Fat Mass/ Total Fat-free Mass Ratio | Baseline | 1.0 Arbitrary units (ratio) | Standard Error 0.07 |
Primary
Body Weight
body weight reported in Kg at at baseline and at 16 weeks in both groups
Time frame: 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide | Body Weight | Baseline | 107.8 Kg | Standard Error 7.7 |
| Semaglutide | Body Weight | 16 weeks | 99.7 Kg | Standard Error 7.2 |
| Standard of Care Only | Body Weight | Baseline | 100.0 Kg | Standard Error 6.7 |
| Standard of Care Only | Body Weight | 16 weeks | 97.1 Kg | Standard Error 7.5 |
Secondary
Total Fat-free Mass (Lean Mass)
total fat-free mass (lean mass) reported in Kg and measured using DEXA at baseline and at 16 weeks in both groups
Time frame: 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide | Total Fat-free Mass (Lean Mass) | baseline | 51.0 Kg | Standard Error 4.2 |
| Semaglutide | Total Fat-free Mass (Lean Mass) | 16 weeks | 49.5 Kg | Standard Error 4 |
| Standard of Care Only | Total Fat-free Mass (Lean Mass) | baseline | 47.8 Kg | Standard Error 2.2 |
| Standard of Care Only | Total Fat-free Mass (Lean Mass) | 16 weeks | 47.0 Kg | Standard Error 2.4 |
Secondary
Total Fat Mass
total fat mass reported in Kg and measured using DEXA at baseline and at 16 weeks in both groups
Time frame: 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide | Total Fat Mass | Baseline | 52.1 Kg | Standard Error 3.6 |
| Semaglutide | Total Fat Mass | 16 weeks | 46.8 Kg | Standard Error 3.6 |
| Standard of Care Only | Total Fat Mass | Baseline | 47.8 Kg | Standard Error 3.9 |
| Standard of Care Only | Total Fat Mass | 16 weeks | 46.3 Kg | Standard Error 4.1 |