Comparison of Differencens in VO2-max, Perfusion of the Heart and Brain and Cognitive Performance Between Patients with Type 2 Diabetes and Healthy Age Matched Controls.

NCT06628297 | Not Yet Recruiting DMC

• 1 other identifier: PhD2024013-HF
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Yet, the majority of elderly patients with ischemic heart disease do not have large-vessel heart disease and it seems that small vessel disease (SVD) may explain a large fraction of these cases as well as the cardiovascular morbidity in the elderly. Hence, the current development in diagnostics and treatments of ischemic heart disease does not address the most common subtype of ischemic disease seen in elderly patients. It has been suggested that SVD is part of a multisystem disorder and several systematic reviews have addressed the hypothesis of a potential link between small vessel disease of the heart, brain, and kidneys. Cerebral SVD is prevalent in the aging population causing cognitive impairment, dementia, and an increased risk of stroke, and cerebral hypoperfusion is an acknowledged cause of vascular dementia and a possible cause of Alzheimer's disease. Further, cognitive impairment within multiple cognitive domains is highly prevalent in heart failure and is associated to an increased risk of dementia. The link between heart failure and dementia may be due to multisystem SVD, although a direct link between the two is possible. Among other known risk factors such as age, hypertension, and female sex, diabetes is a major cause of SVD and is linked to coronary heart disease as well as cognitive impairment. The diagnosis of cerebral SVD relies on MRI detecting infarctions, haemorrhages, microbleeds and ischemic white matter changes, i.e. Fazekas score. In contrast, perfusion PET is used to image myocardial perfusion in patients with coronary SVD; and coronary SVD is recognized as a part of the pathophysiology in angina, coronary artery disease, and heart failure. Perfusion PET before and after adenosine-induced vasodilation allows for measuring, the myocardial flow reserve (MFR), i.e. perfusion capacity, which in the absence of regional perfusion defects, is a measure of coronary SVD. Prof. Eva Prescott have recently shown that reduced MFR obtained by 82Rb PET is a strong predictor of future microvascular events and all-cause mortality. Exercise is well known to improve cognitive health but professor Carl-Johan Boraxbekk has shown that the effect on cognitive performance may be dependent on the initial cerebrovascular status, as patients with moderate to severe white matter changes did not improve after a 6 months physical activation intervention in contrast to patients with mild changes. Yet, it is possible to improve brain function in diabetic patients through either dietary or exercise interventions. Systemic SVD is measured as cerebral SVD (reduced brain perfusion during acetazolamide-induced vasodilation) and coronary SVD (reduced heart perfusion during adenosine-induced vasodilation). The researchers anticipate that patients with type 2 dabetes have reduced perfusion capacity of the brain and heart correlating to reduced cognition and cardiorespiratory fitness (VO2-max).

Conditions

Microvascular Disease; Microvascular Complications; Dementia; Diabetes Mellitus Type 2; Cerebral Hypoperfusion

Keywords

microvascular disease; microvascular complications of the heart; microvascular complications of the brain; diabetes type 2; dementia; microvascular disease patophysiology

Outcome Measures

Primary Outcomes (2)

• [15O]H2O PET assessment of the blood perfusion to the brain

  We will use the scan to determine our primary outcome: Blood perfusion to the brain. Radioactive water (\[15O\]H2O) will be used as a PET-tracer since it follows the blood and is the gold standard tracer for PET-based blood perfusion measurements. We measure the blood perfusion of both the brain as the perfusion capacity, meaning the difference between blood perfusion to the organ at rest and the maximally possible perfusion. In the brain we use injection of diamox to stimualte maximal dilation of the cerebral arteries which corresponds to the maximally possible perfusion of the brain.

  From baseline testing to end of study, 6 months

• [15O]H2O PET assessment of the blood perfusion of the heart

  We will use the scan to determine our primary outcome: Blood perfusion to the heart. Radioactive water (\[15O\]H2O) will be used as a PET-tracer since it follows the blood and is the gold standard tracer for PET-based blood perfusion measurements. We measure the blood perfusion of both the heart as the perfusion capacity, meaning the difference between blood perfusion to the organ at rest and the maximally possible perfusion. In the heart we use injection of adenosin to stimualte maximal dilation of the coronary arteries which corresponds to the maximally possible perfusion of the heart.

  From baseline testing to end of study, 6 months

Secondary Outcomes (3)

• Cognitive performance (CANTAB)

  From baseline testing to end of study, 6 months

• Cognitive Performance (SCIP-D)

  From baseline testing to end of study, 6 months

• Cardiorespiratory fitness (VO2-max)

  From baseline testing to end of study, 6 months

Study Arms (2)

48 patients with type 2 diabetes and increased risk of microvascular disease

Baseline measurements of: * \[15O\]H2O PET of heart and brain * Blood sampling * Echocardiography * Brain MRI * Cognitive tests * Cardiorespiratory fitness test * Muscular function test

Diagnostic Test: PET

24 healthy age-matched participants

Baseline measurements of: * \[15O\]H2O PET of heart and brain * Blood sampling * Echocardiography * Brain MRI * Cognitive tests * Cardiorespiratory fitness test * Muscular function test

Diagnostic Test: PET

Interventions

PET DIAGNOSTIC_TEST

PET imaging will be performed with a Discovery 710 PET/CT scanner (GE Healthcare, Milwaukee, WI, USA). Four 5-minute PET recordings will be performed of each subject within a single scanning session of 70 min. Two consecutive 5-minute scans are conducted of the heart and brain in rest. \[15O\]H2O, is produced on-site (GENtrace, GE, Uppsala, Sweden), and 600 MBq \[15O\]H2O is intravenously injected by an automatic Hidex Radiowater Generator (Hidex, Turku, Finland). To induce heart vasodilation, adenosine is infused (140 g/kg/min) for 6 min and a scan of the heart is repeated. To induce brain vasodilation, 1 g of acetazolamide is infused over 5 min and 15 min later the brain is scanned. Myocardial perfusion is calculated using CarimasCE software version 1.3.1. (Turku, Finland). Cerebral perfusion is calculated using PMOD software (PMOD Technologies, Switzerland).

Also known as: MRI, VO2-max, cognitive testing

24 healthy age-matched participants; 48 patients with type 2 diabetes and increased risk of microvascular disease

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes with increased risk of microvascular disease.

You may qualify if:

• Diabetes type II diagnose with one of the following:
• Duration over 5 years
• Moderate microalbuminuria
• Non-proliferative diabetic retinopathy
• Speaks and understands Danish (required for reliable cognitive testing)
• Able to provide informed and written consent

You may not qualify if:

• Moderate to high intensity training \>1 times/week.
• Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF \<45%), asthma.
• Previous stroke or significant neurological disease including cognitive dysfunction.
• Ongoing depression.
• Hypothyroidism
• Unable or unwilling to participate in training, e.g., due to injury, arthrosis or lung disease.
• Age \> 60 years
• No diagnosis of T2D according to WHO\'s criteria.
• Speaks and understands Danish (required for reliable cognitive testing)
• Able to provide informed and written consent
• Moderate to high intensity training \>2 times/week.
• Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF \<45%), asthma.
• Previous stroke or significant neurological disease including cognitive dysfunction.
• Ongoing depression.
• Hypothyroidism

Sponsors & Collaborators

• University Hospital Bispebjerg and Frederiksberg: lead
• Danish Cardiovascular Academy: collaborator
• Bispebjerg Hospital: collaborator
• The Dagmar Marshall Foundation: collaborator
• Steno Diabetes Center Copenhagen: collaborator

Study Sites (1)

Bispebjerg and Frederiksberg Hospital

Copenhagen, 2400, Denmark

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

We will keep bllod samples in a Biobank. Currently, the relevant tests are not available yet. But once they are, we will use the blood samples to look at markers of neurological damage and inflammation and are associated with dementia.

MeSH Terms

Conditions

Dementia; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Thomas EHJ Primary Investigator, Medical Doctor

  University Hospital Bispebjerg and Frederiksberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Primary Investigator, Medical Doctor

CONTACT

4551903442; thomasehlighjermindjustesen@regionh.dk

Lisbeth Marner, Ph.d.

CONTACT

4591171938; lisbeth.marner@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 4, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)