Dose-response Relationship Between Exercise and Health Outcomes
Primary Purpose
Mitochondrial Function, Glucose Intolerance
Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Exercise
Sponsored by
About this trial
This is an interventional basic science trial for Mitochondrial Function
Eligibility Criteria
Inclusion Criteria:
* Healthy
Exclusion Criteria:
- Endurance training of more than 5 hours a week
- regularly performing high intensity interval training (HIIT).
- Chronic medication,
- chronic diseases.
Sites / Locations
- The Swedish School of Sport and Health Sciences (GIH)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Exercise
Arm Description
Progressive exercise training
Outcomes
Primary Outcome Measures
Change in mitochondrial respiration
Measurement of mitochondrial oxygen consumption in isolated mitochondria from Vastus Lateralis. Respiration will be assessed using substrate combinations targeting both complex I and II. Assessment will be performed in an Oroboros oxygraph
Secondary Outcome Measures
Change in glucose tolerance
Measurement of blood glucose response to 75g oral glucose
Change in oxidative stress
Measurement of carboylated proteins in skeletal muscle biopsies using a commercial ELISA kit
Full Information
NCT ID
NCT04753021
First Posted
February 4, 2021
Last Updated
April 11, 2023
Sponsor
The Swedish School of Sport and Health Sciences
Collaborators
Swedish Research Council for Sport Science
1. Study Identification
Unique Protocol Identification Number
NCT04753021
Brief Title
Dose-response Relationship Between Exercise and Health Outcomes
Official Title
Dose-response Relationship Between Exercise and Health Outcomes
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
February 2, 2018 (Actual)
Primary Completion Date
November 11, 2020 (Actual)
Study Completion Date
March 23, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Swedish School of Sport and Health Sciences
Collaborators
Swedish Research Council for Sport Science
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this study 11 healthy volunteers will perform high intensity exercise training during 4 weeks. The exercise frequency will increase progressively during the first three weeks, followed by a fourth week with lower exercise frequency. 5 skeletal muscle biopsies will be donated throughout the study and 4 oral glucose tolerance tests will be performed after each training period.
Detailed Description
11 healthy and recreational active subjects will be recruited to the study. For inclusion and assessment of baseline physiological characteristics during cycling, a pre-test will be performed on a cycle ergometer and the submaximal and maximal response to exercise will be determined by measurement of respiratory gas exchange. The physiological response to submaximal work rate will be comprised of a series of five minutes long intervals separated with one minutes of rest with assessment of capillary blood lactate and glucose at the end of each workload. All physiological tests and training (HII) sessions will be carefully supervised by trained personnel. The intervention period will include 14 HIIT-sessions in total, all performed at the laboratory under close surveillance and careful monitoring of power output and heart rate. During HIIT sessions, VO2, CO2, blood glucose, lactate and rating of perceived exhaustion (BORG) will be measured.
Energy intake will be standardized for each subject during the day of test sessions. After each HIIT-session a recovery drink containing 1 g · kg-1 bw of carbohydrates and 0.25 g · kg-1 bw of protein will be ingested by the subjects. After HIIT sessions, subjects will be supplied with an evening meal consisting of 74 g carbohydrates, 38 g protein and 26 g fat to be consumed two hours post exercise. Subjects will thereafter remain fasted until the next morning for an oral glucose tolerance test (OGTT) and donation of a muscle biopsy.
All biopsies will be collected in fasted state in early morning following 14 hour of rest after the last HIIT-session. Biopsies will be taken from vastus lateralis in alternating leg in randomized order.
Each subject will complete four OGTTs throughout the study. Resting metabolic rate (RMR) will be measured in supine position by gas exchange measurement using mixing chamber method (Oxycon Pro) attached to a ventilated hood. Thereafter the muscle biopsy will be taken and a catheter will be inserted into the antecubital vein of the forearm. After 10 minutes of passive rest 75 mg glucose dissolved in 300 ml water will be ingested and at 0, 15, 30, 45, 60 75, 90, 105- and 120-minutes after glucose intake a venous blood sample will be taken and instantly analyzed for glucose with enzymatic method in the Biosen C-Line Clinic. Additional RMR measurements will be performed at ~40 and 115 minutes after glucose ingestion.
Mitochondria will be isolated from fresh skeletal muscle biopsies. Mitochondrial respiration and H2O2 emission will be measured using a two-channel high-resolution respirometer with an attached fluorescent probe (Oxygraph-2k, Oroboros Instruments Corporation, Innsbruck, Austria).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Function, Glucose Intolerance
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Exercise
Arm Type
Experimental
Arm Description
Progressive exercise training
Intervention Type
Other
Intervention Name(s)
Exercise
Intervention Description
Progressively increasing training load
Primary Outcome Measure Information:
Title
Change in mitochondrial respiration
Description
Measurement of mitochondrial oxygen consumption in isolated mitochondria from Vastus Lateralis. Respiration will be assessed using substrate combinations targeting both complex I and II. Assessment will be performed in an Oroboros oxygraph
Time Frame
At baseline (before exercise training), after 1 week of training, after 2 weeks of training, after 3 weeks of training, after 4 weeks of training
Secondary Outcome Measure Information:
Title
Change in glucose tolerance
Description
Measurement of blood glucose response to 75g oral glucose
Time Frame
At baseline (before exercise training), after 1 week of training, after 3 weeks of training, after 4 weeks of training
Title
Change in oxidative stress
Description
Measurement of carboylated proteins in skeletal muscle biopsies using a commercial ELISA kit
Time Frame
At baseline (before exercise training), after 1 week of training, after 2 weeks of training, after 3 weeks of training, after 4 weeks of training
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
* Healthy
Exclusion Criteria:
Endurance training of more than 5 hours a week
regularly performing high intensity interval training (HIIT).
Chronic medication,
chronic diseases.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip J Larsen, PhD
Organizational Affiliation
The Swedish School of Sport and Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Swedish School of Sport and Health Sciences (GIH)
City
Stockholm
ZIP/Postal Code
114 86
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36333619
Citation
Flockhart M, Nilsson LC, Ekblom B, Larsen FJ. A Simple Model for Diagnosis of Maladaptations to Exercise Training. Sports Med Open. 2022 Nov 4;8(1):136. doi: 10.1186/s40798-022-00523-x.
Results Reference
derived
PubMed Identifier
33740420
Citation
Flockhart M, Nilsson LC, Tais S, Ekblom B, Apro W, Larsen FJ. Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers. Cell Metab. 2021 May 4;33(5):957-970.e6. doi: 10.1016/j.cmet.2021.02.017. Epub 2021 Mar 18.
Results Reference
derived
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Dose-response Relationship Between Exercise and Health Outcomes
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