Clinical trial NCT04234009: Lifestyle and Brain Vascular Function
Official title: The Effects of a Healthy Lifestyle Intervention on Brain Vascular Function in Older People
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy Lifestyle
Physical Exercise
Healthy Diet
Cerebrovascular Circulation
Cerebral Blood Flow
Glucose Metabolism
Cognitive Performance
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2020-01-21
Enrollment: 10
Sex: ALL
Minimum age (years): 55
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cognitive performance is negatively related to an impaired glucose metabolism, possibly due to impairments in brain vascular function. Supported by the statement from the American Heart and Stroke Association that a healthy lifestyle is one of the most effective strategies to protect against cognitive decline, the investigators now hypothesise that healthy lifestyle intervention-induced changes in glucose metabolism cause beneficial effects on brain vascular function thereby improving cognitive performance. The primary objective of this intervention study is thus to evaluate in sedentary older men and women the effect of a 16-week aerobic-based exercise program on cerebral blood flow, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI) perfusion method Arterial Spin Labeling (ASL). Cerebral blood flow is a robust and sensitive physiological marker of brain vascular function. Secondary objectives are to examine effects on glucose metabolism using the homeostatic model assessment for insulin resistance (HOMA-ir) and cognitive performance as assessed with a neurophysiological test battery.


Eligibility criteria: Inclusion Criteria:

* BMI between 25-35 kg/m2
* Sedentary (assessed as low physically active using the International Physical Activity Questionnaire)
* Right handedness and footedness
* Fasting plasma glucose \< 7.0 mmol/L
* Fasting serum total cholesterol \< 8.0 mmol/L
* Fasting serum triacylglycerol \< 4.5 mmol/L
* Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 100 mmHg
* Stable body weight (weight gain or loss \< 3 kg in the past three months)
* Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
* No difficult venipuncture as evidenced during the screening visit

Exclusion Criteria:

* Current smoker, or smoking cessation \< 12 months
* Diabetic patients
* Familial hypercholesterolemia
* Abuse of drugs
* Consumption of more than 21 alcoholic units/week (men), or more than 14 alcoholic units/week (women)
* Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators
* Use medication to treat blood pressure, lipid or glucose metabolism
* Use of an investigational product within another biomedical intervention trial within the previous 1-month
* Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
* Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
* Contra-indications for MRI imaging, including permanent facial makeup, surgical clips/material in body, metal splinter in eye or claustrophobia

Primary outcomes:
measure: Brain vascular function
timeFrame: Baseline (0 weeks)
measure: Brain vascular function
timeFrame: After intervention (16 weeks)
Secondary outcomes:
measure: Cognitive performance
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Glucose metabolism
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Other outcomes:
measure: Flow-Mediated Vasodilation (FMD)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Carotid Artery Reactivity (CAR)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Pulse Wave Analysis (PWA)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Pulse Wave Velocity (PWV)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Retinal microvascular calibers
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Blood pressure (systolic, diastolic and mean pressure)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Serum lipid profile concentration
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Serum insulin concentration
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Plasma glucose concentration
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Homeostatic Model Assessment for Insulin Resistance (HOMA-ir)
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Circulating markers for low-grade systemic inflammation
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Circulating markers for microvascular function
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Circulating marker of neurogenesis
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Glycated haemoglobin (HbA1C)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Aerobic fitness
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Physical fitness (1)
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Physical fitness (2)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Activity monitoring
timeFrame: Baseline (0 weeks) and after intervention (16 weeks) for four consecutive days
measure: Self reported physical activity
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Food frequency questionnaire
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Dutch Healthy Diet index 2015
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Quality of Life score
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Sleep characteristics
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Fat mass
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Fat free mass
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Anthropometrics (1)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Anthropometrics (2)
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Anthropometrics (3)
timeFrame: Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
measure: Structural brain status (1)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Structural brain status (2)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
measure: Structural brain status (3)
timeFrame: Baseline (0 weeks) and after intervention (16 weeks)
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University
name: Peter J. Joris, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University
name: Ronald P. Mensink, Dr
role: PRINCIPAL_INVESTIGATOR
References: