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

Liverpool John Moores University

Status: Completed

Conditions: Pre-diabetes

Treatments: Diagnostic Test: VO2 Max; Diagnostic Test: Continuous Glucose Monitor; Diagnostic Test: Hyperinsulinaemic Euglycaemic Clamp; Diagnostic Test: MRI; Diagnostic Test: DXA; Procedure: Muscle Biopsies; Other: Exercise Program; Drug: Acipimox 250 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT03809793

250408

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 25 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 2 patient groups, including a placebo group

Acipimox ingestion

Active Comparator group

Description:

Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor), muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest 250 mg of Acipimox 1 hour before each exercise session of the 12 week intervention.

Treatment:

Other: Exercise Program

Drug: Acipimox 250 MG

Diagnostic Test: Continuous Glucose Monitor

Diagnostic Test: MRI

Procedure: Muscle Biopsies

Diagnostic Test: DXA

Diagnostic Test: VO2 Max

Diagnostic Test: Hyperinsulinaemic Euglycaemic Clamp

No drug

Placebo Comparator group

Description:

Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor) with muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest nothing prior to their exercise sessions during the 12-week exercise programme.

Treatment:

Other: Exercise Program

Diagnostic Test: Continuous Glucose Monitor

Diagnostic Test: MRI

Procedure: Muscle Biopsies

Diagnostic Test: DXA

Diagnostic Test: VO2 Max

Diagnostic Test: Hyperinsulinaemic Euglycaemic Clamp