NCT03809793

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 7, 2019

Completed
11 days until next milestone

First Posted

Study publicly available on registry

January 18, 2019

Completed
12 months until next milestone

Study Start

First participant enrolled

January 6, 2020

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2023

Completed
Last Updated

January 3, 2024

Status Verified

December 1, 2023

Enrollment Period

3.6 years

First QC Date

January 7, 2019

Last Update Submit

December 29, 2023

Conditions

Pre-diabetes

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Sub-maximal VO2 walking test

    A change in aerobic capacity (VO2) from baseline will be compared to week 12.

  • Percentage of Liver Fat

    The change percentage of liver fat will be measured at baseline and be compared to value at the end of week 12.

  • Changes in Intramuscular GLUT4

    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.

  • Change in intramuscular DAGs

    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.

Study Arms (2)

Acipimox ingestion

ACTIVE COMPARATOR

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.

Other: Exercise ProgramDiagnostic Test: DXADiagnostic Test: MRIDiagnostic Test: Hyperinsulinaemic Euglycaemic ClampDiagnostic Test: VO2 MaxDiagnostic Test: Continuous Glucose MonitorProcedure: Muscle BiopsiesDrug: Acipimox 250 MG

No drug

PLACEBO COMPARATOR

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.

Other: Exercise ProgramDiagnostic Test: DXADiagnostic Test: MRIDiagnostic Test: Hyperinsulinaemic Euglycaemic ClampDiagnostic Test: VO2 MaxDiagnostic Test: Continuous Glucose MonitorProcedure: Muscle Biopsies

Interventions

Exercise ProgramOTHER

12-week walking based intervention (3 sessions per week)

Acipimox ingestionNo drug
DXADIAGNOSTIC_TEST

Participants will undergo an assessment of body composition (DXA)

Acipimox ingestionNo drug
MRIDIAGNOSTIC_TEST

used to measure fat stored in the liver

Acipimox ingestionNo drug
Hyperinsulinaemic Euglycaemic ClampDIAGNOSTIC_TEST

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.

Acipimox ingestionNo drug
VO2 MaxDIAGNOSTIC_TEST

Assessment of maximum aerobic capacity.

Acipimox ingestionNo drug
Continuous Glucose MonitorDIAGNOSTIC_TEST

CGM sensor will be inserted to measure insulin sensitivity over a 24hr period.

Acipimox ingestionNo drug
Muscle BiopsiesPROCEDURE

Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis.

Acipimox ingestionNo drug
Acipimox 250 MGDRUG

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.

Acipimox ingestion

Eligibility Criteria

Age25 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Liverpool John Moores University

Liverpool, Merseyside, L18 8EU, United Kingdom

Location

MeSH Terms

Conditions

Glucose Intolerance

Interventions

Resistance Trainingacipimox

Condition Hierarchy (Ancestors)

HyperglycemiaGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Exercise TherapyRehabilitationAftercareContinuity of Patient CarePatient CareTherapeuticsPhysical Therapy ModalitiesPhysical Conditioning, HumanExerciseMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Jennifer s Barrett, PhD

    Liverpool John Moores University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
both participants and investigators will know if they are ingesting Acipimox or nothing.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: 34 pre-diabetics will be split into 2 groups; one will ingest Acipimox for 12-weeks and the other will ingest nothing.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PhD researcher in Exercise Metabolism

Study Record Dates

First Submitted

January 7, 2019

First Posted

January 18, 2019

Study Start

January 6, 2020

Primary Completion

July 31, 2023

Study Completion

July 31, 2023

Last Updated

January 3, 2024

Record last verified: 2023-12

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)