The Effect of Exercise on the Brain in Type 2 Diabetes (SAINT)

The Effect of Exercise of High vs. Moderate Intensity on the Brain in Type 2 Diabetes

The goal of this clinical trial is to learn if exercise training of high or moderate intensity is most optimal to improve brain health and prevent neurodegeneration in type 2 diabetes patients. The main question it aims to answer is:

What is the effect of exercise training of high vs. moderate intensity on brain metabolism, brain perfusion, and cognition in type 2 diabetes?

Researchers will compare the exercise training groups to a control group without exercise training to determine the effect of exercise training on the brain in type 2 diabetes.

Participants will exercise for 6 months, 3 times per week. Before and after these 6 months, they will undergo:

• a brain MRI scan
• cognitive tests
• blood sampling

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: Exercise intervention

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominique Hansen, Full professor; Phone Number: +3211292126; Email: dominique.hansen@uhasselt.be
• Study Contact Backup: Name: Jitske Vandersmissen, PhD student; Phone Number: +3211268387; Email: jitske.vandersmissen@uhasselt.be

Study Locations

• Belgium
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Recruiting
      • Hasselt University
      • Contact: Dominique Hansen, Full professor; Phone Number: +3211292126; Email: dominique.hansen@uhasselt.be
      • Contact: Koen Cuypers, Assistant professor; Phone Number: +3211269316; Email: koen.cuypers@uhasselt.be
      • Sub-Investigator: Jitske Vandersmissen, PhD student
      • Sub-Investigator: Robin Heemels, PhD student
      • Sub-Investigator: Melina Hehl, PhD
      • Sub-Investigator: Ilse Dewachter, Full professor
      • Principal Investigator: Koen Cuypers, Assistant professor
      • Sub-Investigator: Stefan Sunaert, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• type 2 diabetes
• no insulin therapy
• 30-75 years old
• physically inactive

Exclusion Criteria:

• MRI contraindications
• psychological disorders
• exogenous insulin therapy
• history of coma, transient ischemic attack, head trauma, brain tumor, stroke, epilepsy, and other central nervous system diseases that could cause dementia or presence of dementia before T2DM
• suffering from any disease with significant impact on exercise intervention participation such as: chronic heart disease (e.g. valve insufficiency ≥ grade 2) or significant arrhythmias, cardiac events less than one year ago (myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention), clinical heart failure (oedema, shortness of breath), percutaneous coronary intervention less than one year ago, chronic obstructive pulmonary disease (COPD), cerebrovascular or peripheral vascular disease
• severe hypertension (>160/110 mmHg)
• ongoing cancer, severe neuropathy (limiting exercise participation)
• renal disease (GRF <45 ml/min/1,73 m2)
• inability to regularly participate in the exercise intervention
• pregnancy
• breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High intensity exercise training group; This arm will receive 6 months of exercise training at high intensity (105% VT2)	Other: Exercise intervention; The exercise intervention entails 6 months of supervised exercise on a hometrainer at high or moderate intensity, 3 times per week
Experimental: Moderate intensity exercise training group; This arm will receive 6 months of exercise training at moderate intensity (60% VT2)	Other: Exercise intervention; The exercise intervention entails 6 months of supervised exercise on a hometrainer at high or moderate intensity, 3 times per week
No Intervention: Control group; This arm won't receive exercise training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurometabolite levels	Levels of N-acetylaspartate, choline, myo-inositol, creatine, glutathion, and glutamate, measured in institutional units (i.u.) by means of magnetic resonance spectroscopy (MRS).	From enrollment to the end of treatment at 6 months
Changes in arterial spin labelling measured by means of magnetic resonance imaging (MRI)	Changes in cerebral perfusion expressed in mL/100g/min, and blood flow through the blood-brain-barrier expressed in milliseconds	From enrollment to the end of treatment at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of neurodegenerative blood biomarkers	Tau (pg/mL), amyloid beta (pg/mL), S100B (ng/mL), neurofilament light (pg/mL) etc.	From enrollment to the end of treatment at 6 months
Blood lipid profile	This outcome measure includes assessments of the lipid profile, reported in milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L): High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), Triglycerides, Free Fatty Acids, Total Cholesterol	From enrollment to the end of treatment at 6 months
Brain volume	Total and regional (LHIPP, mPFC, PCC) brain volumes	From enrollment to the end of treatment at 6 months
Diffusion-weighted magnetic resonance imaging	DWI will be used to measure differences in Brownian motion of water molecules within the brain	From enrollment to the end of treatment at 6 months
Fasted blood glucose	Fasting Glucose: Reported in milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L).	From enrollment to the end of treatment at 6 months
Kidney function (eGFR)	Estimated Glomerular Filtration Rate (eGFR): Reported in milliliters per minute per 1.73 m² (mL/min/1.73 m²).	From enrollment to the end of treatment at 6 months
Cognitive function: MoCA	Cognitive function as assessed by the Montreal Cognitive Assessment (MoCA), scored on a scale of 0-30.	From enrollment to the end of treatment at 6 months
Cognitive function: Face recognition test	Cognitive function as assessed by the Face Recognition Test, reported as the number of correct identifications.	From enrollment to the end of treatment at 6 months
Cognitive function: Object location test	Cognitive function as assessed by the Object Location Test, reported as the number of correct placements.	From enrollment to the end of treatment at 6 months
Cognitive function: Trail making test	Cognitive function as assessed by the Trail Making Test, reported as time to completion (seconds) for Parts A and B.	From enrollment to the end of treatment at 6 months
Cognitive function: Stroop colour and word test	Cognitive function as assessed by the Stroop Color and Word Test, reported as time to completion (seconds) or number of errors.	From enrollment to the end of treatment at 6 months
Cognitive function: Rey auditory verbal learning test	Cognitive function as assessed by the Rey Auditory Verbal Learning Test, reported as the number of words recalled.	From enrollment to the end of treatment at 6 months
Subjective cognitive function	Cognitive function as assessed by the Cognitive Failure Questionnaire, scored on a scale of 0-100.	From enrollment to the end of treatment at 6 months
Peak load during CPET	The maximum load achieved during cardiopulmonary exercise testing (CPET) on a bicycle, measured in watts.	From enrollment to the end of treatment at 6 months
VO2peak during CPET	The peak oxygen consumption measured during CPET, indicating the maximal capacity for oxygen utilization during exercise. Unit of Measure: Milliliters per kilogram per minute (mL/kg/min).	From enrollment to the end of treatment at 6 months
Fasted blood HbA1c	Hemoglobin A1c (HbA1c): Reported as a percentage (%).	From enrollment to the end of treatment at 6 months
Fasting insulin	Fasting Insulin: Reported in micro-international units per milliliter (μIU/mL) or picomoles per liter (pmol/L).	From enrollment to the end of treatment at 6 months
Kidney function (creatinine)	Creatinine: Reported in milligrams per deciliter (mg/dL) or micromoles per liter (μmol/L).	From enrollment to the end of treatment at 6 months

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Jessa Hospital; Research Foundation Flanders
• Investigators: Principal Investigator: Dominique Hansen, Full professor, Hasselt University; Principal Investigator: Koen Cuypers, Assistant professor, Hasselt University

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: dementia; cognition; type 2 diabetes; brain; exercise intervention; cerebral perfusion; neurometabolism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Dementia
• Other Study ID Numbers: B1152024000012; 1129225N (Other Grant/Funding Number: FWO (Fonds Wetenschappelijk Onderzoek)); BOF24KP05 (Other Grant/Funding Number: BOF (Bijzonder Onderzoeksfonds))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No