Can Brisk Walking Combined With Ingestion of a Lipid-lowering Drug Improve Fat Metabolism in Muscle?

NCT03804892 | Unknown

• 1 other identifier: 249734
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Briefly, participants will be assessed for their eligibility for the study using an oral glucose tolerance test, which involves drinking a sugary drink followed by a series of small blood samples. If eligible, participants will be asked to take part in a fitness test and then two trials which will involve walking on a treadmill at a steady pace. Before and after the exercise a small piece of muscle will be taken from their thigh under local anaesthesia, as well as several small blood samples. Muscle muscle samples will be assessed for lipid metabolites.

Conditions

Pre Diabetes

Outcome Measures

Primary Outcomes (4)

• Plasma fatty acids levels

  Blood samples will be assessed for the amount of fatty acids in the blood.

  A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.

• Skeletal muscle Diacylglycerol (DAG) levels

  Muscle biopsies will be assessed for lipid metabolites using liquid chromatography-mass spectrometry.

  A change from baseline DAGs to DAGS immediately post and 3 hours post exercise trial.

• Plasma Glycerol levels

  Blood samples will be assessed for the amount of glycerol in the blood throughout the exercise trial.

  A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.

• IMTG utilisation during exercise

  Muscle samples will be analysed using confocal immunofluorescence microscopy for the amount of IMTG within the samples.

  A change in amount of IMTG within the muscle from baseline, to immediately post and 3 hours post the exercise intervention.

Study Arms (2)

Acipimox ingestion

EXPERIMENTAL

Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test. Following this, participants will ingest 250 mg of Acipimox, before undertaking 45 minutes walking on a treadmill. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.

Diagnostic Test: Body Composition; Diagnostic Test: Maximal aerobic fitness test; Diagnostic Test: Oral glucose tolerance test; Other: Muscle biopsy; Other: Blood samples

No drug

OTHER

Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test.Participants will then undergo a 45 minute walk on a treadmill with no Acipimox ingestion. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.

Diagnostic Test: Body Composition; Diagnostic Test: Maximal aerobic fitness test; Diagnostic Test: Oral glucose tolerance test; Other: Muscle biopsy; Other: Blood samples

Interventions

Body Composition DIAGNOSTIC_TEST

Participants undergo a 5 minute body scan to determine their body composition.

Acipimox ingestion; No drug

Maximal aerobic fitness test DIAGNOSTIC_TEST

Participants will complete a walking fitness text until exhaustion to determine maximal aerobic capacity.

Acipimox ingestion; No drug

Oral glucose tolerance test DIAGNOSTIC_TEST

Participants will undergo an OGTT to determine insulin sensitivity.

Acipimox ingestion; No drug

Muscle biopsy OTHER

Participants will give a small muscle sample pre-, immediately post and 3 hours post- the exercise trial to be assessed for lipid metabolites.

Acipimox ingestion; No drug

Blood samples OTHER

Participants will give 16 blood samples, to be assessed for fatty acids in the blood.

Acipimox ingestion; No drug

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 25-55 years
• Overweight or obese (BMI \>28 kg.m-2)
• Have prediabetes
• 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 intending to get pregnant during the study) or currently breast feeding
• Pre-menopausal
• Not currently involved in a weight loss programme or using weight loss medication

You may not qualify if:

• 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 programmes or using weight loss medication
• Diagnosed with chronic kidney disease

Sponsors & Collaborators

• Liverpool John Moores University: lead
• Diabetes UK: collaborator
• Liverpool University Hospitals NHS Foundation Trust: collaborator
• Royal Liverpool University Hospital: collaborator

Study Sites (1)

Liverpool John Moores University

Liverpool, Merseyside, L18 8EU, United Kingdom

Location

MeSH Terms

Conditions

Glucose Intolerance

Interventions

Body Composition; Glucose Tolerance Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biochemical Phenomena; Chemical Phenomena; Metabolism; Body Constitution; Physiological Phenomena; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Specimen Handling; Punctures; Surgical Procedures, Operative

Study Officials

• Jennifer S Barrett, PhD

  Liverpool John Moores University, L3 3AF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD researcher in Exercise Metabolism

Model Details: This study involves 2 trials. Each trial will involve walking for 45 minutes on a treadmill, with muscle biopsies obtained from the thigh before (basal), immediately following (post-exercise) and 3 h post-exercise. Each trial will be identical, except that participants will ingest either Acipimox or a placebo in a double-blind design. Muscle biopsies will be used to examine differences in muscle fat between the two trials

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 15, 2019
• Study Start: October 1, 2019
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)