Dose-response Relationship Between Exercise and Health Outcomes

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.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance; Mitochondrial Function
• Intervention / Treatment: Other: Exercise

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 114 86
    • The Swedish School of Sport and Health Sciences (GIH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; Progressive exercise training	Other: Exercise; Progressively increasing training load

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Measures

Outcome Measure	Measure Description	Time Frame
Change in glucose tolerance	Measurement of blood glucose response to 75g oral glucose	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	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

Collaborators and Investigators

• Sponsor: The Swedish School of Sport and Health Sciences
• Collaborators: Swedish Research Council for Sport Science
• Investigators: Principal Investigator: Filip J Larsen, PhD, The Swedish School of Sport and Health Sciences

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2018
• Primary Completion (Actual): November 11, 2020
• Study Completion (Actual): March 23, 2023

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance
• Other Study ID Numbers: SwedishSchoolSHS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No