Glucagon-like Peptide-1 Agonism With Very Low Calorie Diets

Type 2 Diabetes Mellitus in Obese Clinical Trial

— SemVLCD  

Official title:

The Anabolic Effects of GLP-1 Agonism to Prevent Lean Muscle Losses During Very-low Calorie Diets (VLCDs) for Weight Loss

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05606471
• Other study ID #: 21031
• Status: Recruiting
• Phase: Phase 4
• Start date: September 15, 2021
• Est. completion date: July 28, 2023

Study information

• Verified date: October 2022
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The very-low calorie diet (VLCD) is a highly effective and safe way to rapidly lose significant amounts of weight and dramatically improve blood sugar control in a short period of time (typically 8-12 weeks). It has recently become recommended by the UK National Health Service as a treatment for selected patients with type 2 diabetes. One drawback of VLCD however is the associated loss of skeletal muscle which affects some patients.

Semaglutide is a well-known medication for type 2 diabetes that also improves blood sugar control and facilitates weight loss. Recent research has shown that it may also stimulate muscle growth, meaning it could help to preserve muscle mass during weight loss. Therefore, this research study aims to see whether taking Semaglutide alongside the VLCD reduces the amount of muscle lost, and could improve the long-term outcomes of VLCD.

The study will take place in the Medical School building in the Royal Derby Hospital. Up to 45 participants will be recruited and allocated into one of 3 groups:

1. Semaglutide only

2. VLCD only

3. Combined Semaglutide plus VLCD The study is 12 weeks in duration and consists of four visits including two 6-hour visits, one 4-hour visit and one 30-minute visit. The first visit is a short Preliminary Visit where participants are asked to ingest stable isotope drinks for measurement of muscle growth rates and muscle mass. Food intake and physical activity monitoring will also be commenced.

Visits 1 & 3 are identical and occur at the beginning and end of the 12-week intervention period, respectively. During these visits participants will undergo a Dual-energy X-ray absorptiometry (DXA) scan, a right vastus lateralis muscle ultrasound scan & muscle biopsy, an intravenous glucose tolerance test, electromyography, tests of muscular function, gait & balance, and questionnaires regarding quality of life & physical activity. These visits are expected to last up to 6 hours.

Visit 2 is a shorter visit mid-way through the 12 weeks, lasting approximately 4.5 hours. Participants will undergo another DXA scan and muscle biopsy in addition to having multiple blood tests taken over a 4-hour period to determine muscle protein breakdown rates.

During the 12 weeks, those in the VLCD group will be asked to stick strictly to an 800 kilocalorie very-low calorie diet, whilst those in the Semaglutide group will be required to inject themselves with Semaglutide once a week. Those in the combined group will be asked to do both. All participants will be monitored closely throughout the 12-week period, with regular phone calls and/or emails.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: July 28, 2023
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Confirmed Type 2 Diabetes Mellitus

• Body mass index > 27kg·m-2

• Eligible for VLCD, Semaglutide (or both), within routine practice

• Ability to provide informed consent

Exclusion Criteria:

• BMI > 50kg·m-2

• Current pregnancy or breastfeeding, or intention to fall pregnant within the next 3 months

• Uncontrolled hypertension (blood pressure >200/120mmHg)

• Current treatment with insulin

• Current or recent use of GLP-1 agonists

• Previous adverse reaction to a GLP-1 agonist

• Current or recent involvement in a VLCD programme (within the last 12 months)

• History of >5% weight loss within the preceding 12 months

• Ingestion of exogenous D2O within the preceding 12 months

• Background of clinically significant cardiovascular, cerebrovascular or respiratory disease, neurological disorders or musculoskeletal problems

• History of malignancy undergoing current treatment or palliation

• History of any medical condition contraindicating the use of GLP-1 agonist medication

• Any other medical condition deemed by the investigators to preclude inclusion into the study

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus in Obese

Intervention

Drug:
• Semaglutide Pen Injector [Ozempic]
Glucagon-like peptide 1 (GLP-1) receptor agonist

Dietary Supplement:
• Very-low Calorie Diet
Total meal replacement with a limit of 800 kilocalories per day

Locations

Country	Name	City	State
United Kingdom	University of Nottingham, Royal Derby Hospital Centre	Derby

Sponsors (2)

Lead Sponsor	Collaborator
University of Nottingham	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle protein synthesis rate	Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle	6 weeks
Primary	Muscle protein breakdown rate	Measuring the rate of breakdown of skeletal muscle in vivo using the rate of appearance of deuterium-labelled 3-methyl-histidine in blood after an initial oral bolus	6 weeks
Secondary	Skeletal muscle mass	Determined from DXA scanning (measured in kg and percentage of total body weight) and novel techniques using rate of appearance of a creatine tracer in urine after an initial bolus	12 weeks
Secondary	Fat mass	Determined from DXA scanning (measured in kg and percentage of total body weight)	12 weeks
Secondary	Total body weight	Measured in kg	12 weeks
Secondary	Whole body insulin sensitivity	Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose	12 weeks
Secondary	Pancreatic beta cell function	Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose	12 weeks
Secondary	Skeletal muscle strength	Determined from maximal voluntary contraction (MVC) of left knee extension	12 weeks
Secondary	Skeletal neuromuscular function	Assessed using measurement of force stability during electromyography	12 weeks
Secondary	Gross skeletal muscle function	Measured using a short battery of physical performance tests (SBPPT) to give an overall score of skeletal gross skeletal muscle function (scored out of 12)	12 weeks
Secondary	Right vastus lateralis muscle thickness	Determined from muscle ultrasonography	12 weeks
Secondary	Right vastus lateralis muscle cross sectional area (CSA)	Determined from muscle ultrasonography	12 weeks
Secondary	Right vastus lateralis muscle fibre pennation angle	Determined from muscle ultrasonography	12 weeks