Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug?
Condition: Pre-diabetes
MeSH terms: Prediabetic State
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Exercise Program; DXA; MRI; Hyperinsulinaemic Euglycaemic Clamp; VO2 Max; Continuous Glucose Monitor; Muscle Biopsies; Acipimox 250 MG
Intervention type(s): Other; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Procedure; Drug
Intervention description(s): 12-week walking based intervention (3 sessions per week); Participants will undergo an assessment of body composition (DXA); used to measure fat stored in the liver; 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.; Assessment of maximum aerobic capacity.; CGM sensor will be inserted to measure insulin sensitivity over a 24hr period.; Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis.; 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.
Intervention MeSH terms: Acipimox
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 34 pre-diabetics will be split into 2 groups; one will ingest Acipimox for 12-weeks and the other will ingest nothing.
Masking: None (Open Label)
Primary purpose: Prevention