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Completed

NCT Number: NCT04210869

Mixed Nuts and Brain Vascular Function

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.

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Key information

Age range

60 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University Medical Center

Maastricht, Limburg, 6229 ER, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Mixed Nuts

Dietary Supplement

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.

Primary outcomes

  1. Brain Vascular Function

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)

Secondary outcomes

  1. Brain Insulin Sensitivity

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    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)

  2. Cognitive performance

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Cambridge Neuropsychological Test Automated Battery (CANTAB)

Other outcomes

  1. Glucose metabolism

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Oral Glucose Tolerance Test (OGTT)

  2. Peripheral vascular function (1)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Flow-mediated vasodilation (FMD)

  3. Peripheral vascular function (2)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Carotid artery reactivity (CAR)

  4. Peripheral vascular function (3)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Pulse wave analysis (PWA)

  5. Peripheral vascular function (4)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Pulse wave velocity (PWV)

  6. Peripheral vascular function (5)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Retinal microvascular calibers

  7. Blood pressure

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Office and 24-hour ambulatory blood pressure

  8. Advanced glycation endproducts

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Serum protein-bound advanced glycation endproducts (AGEs)

  9. Blood lipids

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Lipids and Lipoproteins

  10. Blood glucose

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Glucose

  11. Blood insulin

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Insulin

  12. Blood markers for low-grade systemic inflammation

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Markers for low-grade systemic inflammation (IL-6, TNF-alpha)

  13. Blood markers for microvascular function

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Markers for microvascular function (sCAM-1, vWf, cGMP)

  14. Blood marker of neurogenesis

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Brain-derived neurotrophic factor

  15. Parameters for compliance

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Alpha-linoleic acid levels (blood)

  16. Structural brain status

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    MRI Structural MPRAGE scan

  17. Functional connectivity

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Resting and task-induced blood-oxygen-level-dependent (BOLD) response, as quantified by functional MRI T2*-weighted imaging.

  18. Fat distribution in abdomen

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    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).

  19. Microbiota composition

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Fecal samples will be collected to be used for analysing different species of microbiota.

  20. Other perceivable benefits: Quality of Life

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    The Quality of life will be assessed using a 32-item questionnaire

  21. Other perceivable benefits: Sleep characteristics

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index

  22. Other perceivable benefits: Mood

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Mood will be tested using the Affect Grid

  23. Other perceivable benefits: Physical fitness (1)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Timed up-and-go test (TUGT)

  24. Other perceivable benefits: Physical fitness (2)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    The 6-minute walk test (6 MWT)

  25. Other perceivable benefits: Physical fitness (3)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Handgrip test

  26. Other perceivable benefits: Physical fitness (4)

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Muscle strength test, as measured using the Biodex system

  27. Weight

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Weight in kilograms

  28. Length

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Length in meters

  29. Waist circumference

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Waist circumference in centimeters

  30. Hip circumference

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Hip circumference in centimeters

  31. Indirect fat distribution

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Measured by skinfold measurements

  32. Food intake

    Time frame: Change in outcomes at the end of a 16-week mixed nuts intervention and 16-week control period.

    Food intake will be assessed using the Food Frequency Questionnaire

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • The International Nut and Dried Fruit Council (INC)

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Dec 26, 2019
Registry last updated
Jan 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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