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CompletedNCT03329651Updated Nov 9, 2018

The Interaction Between Metformin and Acute Exercise

An interventional study of Metformin treatment and Placebo treatment in Impaired Glucose Tolerance and Diabetes Mellitus, Type 2, sponsored by Kristian Karstoft. Completed at 1 site in Denmark. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-11-09.

Sponsored by Kristian Karstoft · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
34
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

Physical activity is a first line treatment for patients with type 2 diabetes (T2D), however, the vast majority of patients with T2D do not achieve satisfying glycemic control with physical activity alone, which is why pharmacological treatment with metformin is most often initiated.

It is known that metformin and exercise both activates 5' adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle and liver, and the activation of AMPK results in many different metabolic effects, including improvements in glycemic control. Because of this similarity in mechanism of action, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. Thus, the aim of this study is to assess the effects of acute physical activity with and without concomitant metformin treatment, in order to investigate whether an interaction between the two occur.

Subjects with impaired glucose tolerance will be randomized (1:1) to metformin/placebo treatment in a double-blinded way. Following a treatment run-in period of 17 days, two experimental days (one with acute exercise and one without acute exercise), separated by one week, will be performed in each subject.

This registration concerns a sub-study of another study which has previously been registrered at ClinicalTrials.gov (Unique Protocol ID: H-17012307). The specific outcomes in this registration have not previously been registered.

02

Conditions studied

  • Impaired Glucose Tolerance
  • Diabetes Mellitus, Type 2
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Glucose-lowering-medication naïve T2D and/or subjects with impaired glucose tolerance defined as: 2-h plasma glucose (PG) in the 75-g OGTT (7.8-11.0 mmol/L) and/or HbA1c (39-47 mmol/mol)
  • Caucasian
  • BMI > 25 but \< 40 kg/m2
  • Low to moderate physically active (≤90 min of structured physical activity/week)

Exclusion criteria

Exclusion Criteria:

  • Pregnancy
  • Smoking
  • Glucose-lowering treatment
  • Treatment with steroids and other immunomodulating drugs
  • Contraindication to increased levels of physical activity
  • Liver disease (ALAT elevated more than 3 times above upper normal limit, or reduced levels of the liver function markers albumin and KF II+VII+X)
  • Renal insufficiency (eGFR\<60 ml/min)
  • Prior history of lactic acidosis
  • HbA1c >55 mmol/mol and/or 2-hPG in the 75-g OGTT > 15 mmol/L
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
34 participants (actual)

Study arms

  • Experimental
    Metformin treatment

    Drug: Metformin treatment

  • Placebo comparator
    Placebo treatment

    Drug: Placebo treatment

Interventions

  • DrugMetformin treatment

    Daily treatment with metformin tablets for 24 days according to the following scheme: Day 1-4: Metformin tablet 500 mg x 2 Day 5-8: Metformin tablet 1000 + 500 mg Day 9-24: Metformin tablet 1000 mg x 2

  • DrugPlacebo treatment

    Daily treatment with placebo tablets for 24 days according to the following scheme: Day 1-4: Placebo tablet 500 mg x 2 Day 5-8: Placebo tablet 1000 + 500 mg Day 9-24: Placebo tablet 1000 mg x 2

05

What researchers measure

Primary outcomes

  1. Difference in postprandial glycemic control as assessed by mean blood glucose concentration during a 4 hour mixed-meal tolerance test

    Time frame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

Secondary outcomes

  1. Difference in endogenous glucose production as assessed by rate of infused glucose tracer appearance in blood

    Time frame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

  2. Difference in exogenous glucose uptake as assessed by rate of ingested glucose tracer appearance in blood

    Time frame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

  3. Difference in peripheral glucose uptake as assessed by rate of glucose disappearance from blood

    Time frame: Day 17 (no acute exercise [control day]) and 24 (following an acute exercise bout)

06

Study locations

1 site
  • Center for aktiv sundhed
    Copenhagen, Copenhagen N 2200, Denmark
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03329651
Lead sponsor
Kristian Karstoft
Collaborators
University of Copenhagen
Responsible party
Kristian Karstoft (Principal Investigator, Rigshospitalet, Denmark) — Sponsor-investigator
First posted
Nov 6, 2017
Start date
Nov 10, 2017
Primary completion
Jul 1, 2018
Completion
Oct 1, 2018
Last update
Nov 9, 2018

Study contacts

Kristian Karstoft, MD, PhD
principal investigator · Rigshospitalet, Denmark

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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