Mixed Nuts and Brain Vascular Function

Cerebral Blood Flow Clinical Trial

Official title:

The Long-Term Effects of Mixed Nuts Consumption on Brain Vascular Function in Elderly Men and Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04210869
• Other study ID #: METC 19-058
• Status: Completed
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2022
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Impaired brain vascular function precedes the development of reduced cognitive performance, while brain insulin-resistance is also associated with cognitive decline. The Mediterranean diet, which is rich in nuts, may protect against the development of impaired cognitive performance. The hypothesis is that long-term mixed nut consumption increases brain insulin-sensitivity thereby improving brain vascular function and cognitive performance. The primary objective is to evaluate in elderly men and women the effect of 16-week mixed nut consumption on cerebral blood flow, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labelling (ASL). Cerebral blood flow is a robust and sensitive physiological marker of brain vascular function. Secondary objectives are to investigate effects on the cerebral blood flow response to intranasal insulin delivery - a marker of insulin-sensitivity in the human brain - as quantified by ASL, and cognitive functioning as assessed with a neuropsychological test battery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 70 Years

Eligibility

Inclusion Criteria:

• Aged between 60-70 years
• BMI between 25-35 kg/m2
• 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:

• Allergy or intolerance to nuts
• Left-handedness
• Current smoker, or smoking cessation < 12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• More than 3 alcoholic consumptions per day
• Use of products or dietary supplements known to interfere with the main 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 (e.g. pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)

Related Conditions & MeSH terms

• Brain Vascular Function
• Cerebral Blood Flow

Intervention

Dietary Supplement:
• Mixed Nuts
Study volunteers will receive daily 60 g of mixed nuts (15 g walnut, 15 g cashew, 15 g hazelnut, 15 g pistachio) for 16 weeks.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	The International Nut and Dried Fruit Council (INC)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glucose metabolism	Oral Glucose Tolerance Test (OGTT)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Peripheral vascular function (1)	Flow-mediated vasodilation (FMD)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Peripheral vascular function (2)	Carotid artery reactivity (CAR)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Peripheral vascular function (3)	Pulse wave analysis (PWA)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Peripheral vascular function (4)	Pulse wave velocity (PWV)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Peripheral vascular function (5)	Retinal microvascular calibers	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood pressure	Office and 24-hour ambulatory blood pressure	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Advanced glycation endproducts	Serum protein-bound advanced glycation endproducts (AGEs)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood lipids	Lipids and Lipoproteins	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood glucose	Glucose	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood insulin	Insulin	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood markers for low-grade systemic inflammation	Markers for low-grade systemic inflammation (IL-6, TNF-alpha)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood markers for microvascular function	Markers for microvascular function (sCAM-1, vWf, cGMP)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Blood marker of neurogenesis	Brain-derived neurotrophic factor	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Parameters for compliance	Alpha-linoleic acid levels (blood)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Structural brain status	MRI Structural MPRAGE scan	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Functional connectivity	Resting and task-induced blood-oxygen-level-dependent (BOLD) response, as quantified by functional MRI T2*-weighted imaging.	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Fat distribution in abdomen	Magnetic Resonance Imaging measurements will be included to quantify abdominal fat compartments (i.e.; subcutaneous and visceral fat) and fat content of abdominal organs (i.e. liver and pancreas).	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Microbiota composition	Fecal samples will be collected to be used for analysing different species of microbiota.	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Quality of Life	The Quality of life will be assessed using a 32-item questionnaire	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Sleep characteristics	Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Mood	Mood will be tested using the Affect Grid	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Physical fitness (1)	Timed up-and-go test (TUGT)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Physical fitness (2)	The 6-minute walk test (6 MWT)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Physical fitness (3)	Handgrip test	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Other perceivable benefits: Physical fitness (4)	Muscle strength test, as measured using the Biodex system	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Weight	Weight in kilograms	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Length	Length in meters	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Waist circumference	Waist circumference in centimeters	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Hip circumference	Hip circumference in centimeters	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Indirect fat distribution	Measured by skinfold measurements	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Other	Food intake	Food intake will be assessed using the Food Frequency Questionnaire	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Primary	Brain Vascular Function	Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Secondary	Brain Insulin Sensitivity	Change in cerebral blood flow, as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL), before and after application of intranasal insulin (160 IU)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.
Secondary	Cognitive performance	Cambridge Neuropsychological Test Automated Battery (CANTAB)	Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.