Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug?

Pre-diabetes Clinical Trial

Official title:

Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03809793
• Other study ID #: 250408
• Status: Completed
• Phase: N/A
• Start date: January 6, 2020
• Est. completion date: July 31, 2023

Study information

• Verified date: December 2023
• Source: Liverpool John Moores University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study investigates the hypothesis that an exercise programme of steady walking will have larger effects on insulin sensitivity and glycemic control when combined with Acipimox intake prior to each exercise session in people with pre-diabetes. Thirty-four sedentary, overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with pre-diabetes will be recruited using the same strategy as study 2 and split into two groups (detailed below). Participants will undergo several pre- intervention assessments, followed by a 12-week walking based intervention combined with either Acipimox ingestion or no drug ingestion, pre- each exercise session. Following this, the post-assessment measures will identical to the pre-assessment measures.

Description:

Study 3 investigates the hypothesis that an exercise programme of steady walking will have larger effects on insulin sensitivity and glycaemic control when combined with Acipimox intake prior to each exercise session in people with prediabetes. Thirty-four sedentary, overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with prediabetes will be recruited using the same strategy as study 2 and split into two groups (detailed below). Pre-intervention assessments: Visit 1: Participants will undergo an assessment of body composition (DXA) and undertake a graded treadmill walking test to estimate maximal aerobic fitness (VO2max). Visit 2: Participants will be able to opt to undergo an MRI scan, taking place before breakfast. The MRI scan is used to measure fat stored in the liver and muscles. A continuous glucose monitoring (CGM) sensor will be inserted to measure insulin sensitivity. Visit 3: Participants will arrive at the laboratory after an overnight fast (>10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp. Exercise intervention: Pairs of participants from each group (matched for gender, age and VO2max) will be randomized to undertake 12 weeks of steady walking combined with ingestion of either Acipimox or placebo in a counter-balanced, double-blind design. Supervised treadmill walking sessions will be undertaken at LJMU three times per week, with exercise performed at a speed equivalent to 45% VO2max. Participants will initially exercise for 30 mins per session (weeks 1 and 2), and each session will increase in duration by 5 mins every 2 weeks thereafter, up to 50 minutes of exercise. 1 hour before each walking session, participants will ingest either 250 mg Acipimox or nothing. Post-intervention assessments: The post-intervention assessments will be identical in all respects to the pre-intervention assessments and will be commenced ≥72 hours after the final training session.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 50 Years

Eligibility

Inclusion Criteria:

• BMI >28 kg.m-2
• Pre-diabetic
• Not currently using any anti-diabetes medication
• Physically inactive (performing less than two 30 min structured exercise sessions per week for the last year)
• Not pregnant or currently breast feeding
• Pre-menopausal
• Not currently involved in a weight loss programme or using weight loss medication

Exclusion Criteria:

• Involved in regular exercise (engaged in more than 2 sessions of structured exercise of >30 min per week)
• Currently using anti-diabetes medication (e.g. insulin, metformin)
• Currently using niacin/vitamin B3 supplements
• Pregnant or breast feeding
• Currently engaged in active weight loss programme or using weight loss medication
• Diagnosed with chronic kidney disease

Related Conditions & MeSH terms

• Pre-diabetes
• Prediabetic State

Intervention

Other:
• Exercise Program
12-week walking based intervention (3 sessions per week)

Diagnostic Test:
• DXA
Participants will undergo an assessment of body composition (DXA)
• MRI
used to measure fat stored in the liver
• Hyperinsulinaemic Euglycaemic Clamp
Participants will arrive at the laboratory after an overnight fast (>10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.
• VO2 Max
Assessment of maximum aerobic capacity.
• Continuous Glucose Monitor
CGM sensor will be inserted to measure insulin sensitivity over a 24hr period.

Procedure:
• Muscle Biopsies
Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis.

Drug:
• Acipimox 250 MG
Participants will be randomised into two groups. One group will be prescribed Acipimox that will be taken 1 hour prior to each exercise session. The other group will take no drug.

Locations

Country	Name	City	State
United Kingdom	Liverpool John Moores University	Liverpool	Merseyside

Sponsors (4)

Lead Sponsor	Collaborator
Liverpool John Moores University	Diabetes UK, Liverpool University Hospitals NHS Foundation Trust, Royal Liverpool University Hospital

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Sensitivity	A pre- and post- hyperinsulinaemic euglycaemic clamp will assess changes in whole body insulin sensitivity.	A change in insulin sensitivity from baseline will be compared to week 12.
Secondary	Sub-maximal VO2 walking test	Participants will be assessed for pre- and post- maximal aerobic capacity.	A change in aerobic capacity (VO2) from baseline will be compared to week 12.
Secondary	Percentage of Liver Fat	A pre- and post- intervention MRI scan will show any changes in Liver Fat	The change percentage of liver fat will be measured at baseline and be compared to value at the end of week 12.
Secondary	Changes in Intramuscular GLUT4	Muscle biopsy samples will undergo analysis of mechanisms for insulin sensitivity and lipid metabolites using confocal immunofluorescence microscopy.	A change in the co-localisation of GLUT4 will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.
Secondary	Change in intramuscular DAGs	The amount of DAGs within the muscle will be analysed using liquid chromatography-mass spectrometry.	A change in the amount of DAGs will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.