Mitochondrial FunctionNCT04753021
Dose-response Relationship Between Exercise and Health Outcomes
A study testing Exercise in people with Mitochondrial Function and Glucose Intolerance, run by The Swedish School of Sport and Health Sciences at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Function, Glucose Intolerance
- What is being tested?
- Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteSweden
- Study dates
- 2 Feb 2018to 23 Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
Who cannot join
- Endurance training of more than 5 hours a week
- regularly performing high intensity interval training (HIIT).
- Chronic medication,
- chronic diseases.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
The Swedish School of Sport and Health Sciences (GIH)
Stockholm, 114 86
About this study
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.
Read the 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).
- Conditions
- Mitochondrial Function, Glucose Intolerance
- Being tested
- Exercise
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseOther
Progressively increasing training load
| Study group | Role | What they receive |
|---|---|---|
| Exercise | Experimental | Progressive exercise training Receives: Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 outcomes (2)
Change in glucose tolerance
Measurement of blood glucose response to 75g oral glucose
Measured: At baseline (before exercise training), after 1 week of training, after 3 weeks of training, after 4 weeks of training
Change in oxidative stress
Measurement of carboylated proteins in skeletal muscle biopsies using a commercial ELISA kit
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2021
- Study start2 Feb 2018
- Primary completion11 Nov 2020
- Study completion23 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial FunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Swedish School of Sport and Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Research Council for Sport Science
- Responsible party
- Sponsor
- Investigators
- Filip J Larsen, PhD, Principal investigator, The Swedish School of Sport and Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04753021
- Sponsor's protocol ID
- SwedishSchoolSHS
- Status last verified
- Apr 2023
- First submitted
- 4 Feb 2021
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36333619Flockhart 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.
PubMed 33740420
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-response Relationship Between Exercise and Health Outcomes
- ClinicalTrials.gov ID
- NCT04753021
- Acronym / sponsor ID
- SwedishSchoolSHS
- Conditions
- Mitochondrial Function, Glucose Intolerance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- The Swedish School of Sport and Health SciencesUniversity, hospital or other
- Collaborators
- Swedish Research Council for Sport Science
- Study start
- 2 Feb 2018 (actual)
- Primary completion
- 11 Nov 2020 (actual)
- Study completion
- 23 Mar 2023 (actual)
- First posted
- 12 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exercise | Experimental | Other: ExerciseProgressive exercise training |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy
Key exclusion criteria (4 listed)
- Endurance training of more than 5 hours a week
- regularly performing high intensity interval training (HIIT).
- Chronic medication,
- chronic diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExerciseProgressively increasing training load | Other | Exercise |
Primary outcome
Change in mitochondrial respiration
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
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
2 secondary outcomes
Change in glucose tolerance
Time frame: At baseline (before exercise training), after 1 week of training, after 3 weeks of training, after 4 weeks of training
Change in oxidative stress
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Derived from this study: PubMed 36333619Flockhart 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.
- Derived from this study: PubMed 33740420Flockhart 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filip J Larsen, PhD principal investigator
The Swedish School of Sport and Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise in people with Mitochondrial Function and Glucose Intolerance, run by The Swedish School of Sport and Health Sciences at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mitochondrial respiration (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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04753021, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2023.