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Glucagon-like Peptide-1 Agonism With Very Low Calorie Diets (SemVLCD)

Primary Purpose

Type 2 Diabetes Mellitus in Obese

Status
Recruiting
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Semaglutide Pen Injector [Ozempic]
Very-low Calorie Diet
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus in Obese focused on measuring Type 2 diabetes, Obesity, GLP-1, Semaglutide, VLCD

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Nottingham, Royal Derby Hospital CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

VLCD only

Semaglutide only

Combined VLCD plus Semaglutide

Arm Description

Participants in this group will be placed on a very-low calorie diet with a daily energy intake limit of 800 kilocalories. 600 kilocalories will be made up of total meal replacement products supplied by Lighterlife UK. The remaining 200 kilocalories will be flexible for participants to add additional vegetables to supplement the total meal replacement products, allowing some variety to the diet.

Participants will be asked to self-administer the GLP-1 agonist Semaglutide weekly, as per clinical practice. They will be asked to start at 0.25mg and increase every two weeks (if tolerated) to the maintenance dose of 1mg, which they will continue until the end of the study.

Participants in this group will both partake in the VLCD, and take the weekly dose of Semaglutide (as described above).

Outcomes

Primary Outcome Measures

Muscle protein synthesis rate
Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle
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

Secondary Outcome Measures

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
Fat mass
Determined from DXA scanning (measured in kg and percentage of total body weight)
Total body weight
Measured in kg
Whole body insulin sensitivity
Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose
Pancreatic beta cell function
Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose
Skeletal muscle strength
Determined from maximal voluntary contraction (MVC) of left knee extension
Skeletal neuromuscular function
Assessed using measurement of force stability during electromyography
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)
Right vastus lateralis muscle thickness
Determined from muscle ultrasonography
Right vastus lateralis muscle cross sectional area (CSA)
Determined from muscle ultrasonography
Right vastus lateralis muscle fibre pennation angle
Determined from muscle ultrasonography

Full Information

First Posted
May 23, 2022
Last Updated
October 31, 2022
Sponsor
University of Nottingham
Collaborators
Medical Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT05606471
Brief Title
Glucagon-like Peptide-1 Agonism With Very Low Calorie Diets
Acronym
SemVLCD
Official Title
The Anabolic Effects of GLP-1 Agonism to Prevent Lean Muscle Losses During Very-low Calorie Diets (VLCDs) for Weight Loss
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2021 (Actual)
Primary Completion Date
July 28, 2023 (Anticipated)
Study Completion Date
July 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nottingham
Collaborators
Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief 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: Semaglutide only VLCD only 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus in Obese
Keywords
Type 2 diabetes, Obesity, GLP-1, Semaglutide, VLCD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VLCD only
Arm Type
Active Comparator
Arm Description
Participants in this group will be placed on a very-low calorie diet with a daily energy intake limit of 800 kilocalories. 600 kilocalories will be made up of total meal replacement products supplied by Lighterlife UK. The remaining 200 kilocalories will be flexible for participants to add additional vegetables to supplement the total meal replacement products, allowing some variety to the diet.
Arm Title
Semaglutide only
Arm Type
Active Comparator
Arm Description
Participants will be asked to self-administer the GLP-1 agonist Semaglutide weekly, as per clinical practice. They will be asked to start at 0.25mg and increase every two weeks (if tolerated) to the maintenance dose of 1mg, which they will continue until the end of the study.
Arm Title
Combined VLCD plus Semaglutide
Arm Type
Experimental
Arm Description
Participants in this group will both partake in the VLCD, and take the weekly dose of Semaglutide (as described above).
Intervention Type
Drug
Intervention Name(s)
Semaglutide Pen Injector [Ozempic]
Intervention Description
Glucagon-like peptide 1 (GLP-1) receptor agonist
Intervention Type
Dietary Supplement
Intervention Name(s)
Very-low Calorie Diet
Intervention Description
Total meal replacement with a limit of 800 kilocalories per day
Primary Outcome Measure Information:
Title
Muscle protein synthesis rate
Description
Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle
Time Frame
6 weeks
Title
Muscle protein breakdown rate
Description
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
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Skeletal muscle mass
Description
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
Time Frame
12 weeks
Title
Fat mass
Description
Determined from DXA scanning (measured in kg and percentage of total body weight)
Time Frame
12 weeks
Title
Total body weight
Description
Measured in kg
Time Frame
12 weeks
Title
Whole body insulin sensitivity
Description
Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose
Time Frame
12 weeks
Title
Pancreatic beta cell function
Description
Determined using the intravenous glucose tolerance test and measures of fasting insulin & glucose
Time Frame
12 weeks
Title
Skeletal muscle strength
Description
Determined from maximal voluntary contraction (MVC) of left knee extension
Time Frame
12 weeks
Title
Skeletal neuromuscular function
Description
Assessed using measurement of force stability during electromyography
Time Frame
12 weeks
Title
Gross skeletal muscle function
Description
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)
Time Frame
12 weeks
Title
Right vastus lateralis muscle thickness
Description
Determined from muscle ultrasonography
Time Frame
12 weeks
Title
Right vastus lateralis muscle cross sectional area (CSA)
Description
Determined from muscle ultrasonography
Time Frame
12 weeks
Title
Right vastus lateralis muscle fibre pennation angle
Description
Determined from muscle ultrasonography
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Iskandar Idris
Organizational Affiliation
Professor in Diabetes and Vascular Medicine & Honorary Consultant
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nottingham, Royal Derby Hospital Centre
City
Derby
ZIP/Postal Code
DE22 3DT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philip Atherton, BSc MSc PhD
Phone
01332724622
Email
philip.atherton@nottingham.ac.uk
First Name & Middle Initial & Last Name & Degree
Iskandar Idris
First Name & Middle Initial & Last Name & Degree
Oluwaseun Anyiam
First Name & Middle Initial & Last Name & Degree
Kenneth Smith
First Name & Middle Initial & Last Name & Degree
Beth Phillips
First Name & Middle Initial & Last Name & Degree
Dan Wilkinson

12. IPD Sharing Statement

Plan to Share IPD
No

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

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