Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-04-01 @ 2:43 AM
Study NCT ID:
NCT07422220
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-19
First Post:
2025-10-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Long-Term Effects of Walnut Consumption on Brain Function
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D056128', 'term': 'Obesity, Abdominal'}, {'id': 'D060825', 'term': 'Cognitive Dysfunction'}], 'ancestors': [{'id': 'D009765', 'term': 'Obesity'}, {'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 55}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-02', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2027-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-18', 'studyFirstSubmitDate': '2025-10-02', 'studyFirstSubmitQcDate': '2026-02-18', 'lastUpdatePostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-08', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Endothelial function - Flow Mediated Dilation', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Changes in diameter during Flow-Mediated Dilation (FMD) of the brachial artery will be assessed using ultrasound.'}, {'measure': 'Endothelial function - Carotid Artery Reactivity', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Changes in diameter during Carotid Artery Reactivity (CAR) in response to a cold stressor will be assessed using ultrasound'}, {'measure': 'Markers related to arterial stiffness', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Pulse Wave Analysis (PWA) of the radial artery and Femoral-to-carotid Pulse Wave Velocity (PWV) in m/s will be measured with a tonometer using Sphygomocor'}, {'measure': 'Peripheral insulin sensitivity', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': '7-point oral glucose tolerance test (OGTT) to determine insulin sensitivity based on insulin and glucose concentrations, Matsuda index and 2h glucose tolerance (2h glucose concentrations)'}, {'measure': 'Brain perfusion', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Cerebral blood flow velocity (CBFv) of the medial cerebral artery will be measured with transcranial Doppler ultrasound (TCD)'}, {'measure': 'Markers related to gut microbiota activity', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Fecal and fasting plasma short-chain fatty acids (acetate, butyrate, propionate), fecal bile acids (cholic acid, chenodeoxycholic acid, doxycholic acid, lithocholic acid), fecal lipid (non-esterified fatty acids, triacylglycerides, total cholesterol)'}, {'measure': 'Perceived hunger and satiety', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Visual analogue scales (VAS) questionnaires'}, {'measure': 'Mental health', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Beck Depression Inventory (BDI), State-Trait Anxiety Inventories (STAI)'}, {'measure': 'Mood', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Profile of Mood States (POMS) questionnaire'}, {'measure': 'Stress', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Perceived Stress Scale (PSS) questionnaire'}, {'measure': 'Sleep characteristics', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Pittsburgh Sleep Quality Index (PSQI) questionnaire to assess sleep duration, quality, latency, and efficiency'}, {'measure': 'Office blood pressure', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Office blood pressure and heart rate'}, {'measure': '24h ambulatory blood pressure', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': '24h ambulatory blood pressure measured every 15 min'}, {'measure': 'Lipid metabolism', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks"', 'description': 'Circulating triacylglycerol, High-Density Lipoprotein (HDL) cholesterol, Low-Density Lipoprotein (LDL) cholesterol, and Total Cholesterol concentrations'}, {'measure': 'Markers related to low-grade systemic inflammation', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)a, monocyte chemo attractant protein (MCP)-1, C-reactive protein (hsCRP) and serum amyloid A (SAA)'}, {'measure': 'Markers related to arterial stiffness', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Pulse Wave Velocity (PWV) in m/s measured with a tonometer using Sphygomocor'}, {'measure': 'Structural brain status', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'High-resolution anatomical MPRAGE scan'}, {'measure': 'Body Composition - Fat Mass', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'BodPod will be used to measure fat mass (weight)'}, {'measure': 'Body Composition - Fat Free Mass', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'BodPod will be used to measure fat free mass (weight).'}, {'measure': 'Ad libitum food intake - weight', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Ad libitum food intake (weight) in the fasted state'}, {'measure': 'Ad libitum food intake - Caloric content', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Ad libitum food intake (caloric content) in the fasted state.'}, {'measure': 'Satiety hormones related to food intake', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Plasma levels of GLP-1 before and after ad libitum food intake at time points 0, 15, 30, 60, 90 minutes.'}, {'measure': 'Retinal microvasculature', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Retinal microvascular calibers will be measured using retinal images made with a fundus camera'}, {'measure': 'Weight', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Weight in kilograms'}, {'measure': 'Waist circumference', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Waist circumference in centimeters'}, {'measure': 'Hip circumference', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Hip circumference in centimeters'}, {'measure': 'Food intake', 'timeFrame': 'From enrollment to the end of the intervention at 24 weeks.', 'description': 'Food intake will be assessed using the Food Frequency Questionnaire'}], 'primaryOutcomes': [{'measure': 'Cerebral blood flow (CBF) prior to and after application of intranasal insulin', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks', 'description': 'CBF will be non-invasively measured using the gold-standard methodology pseudo-continuous arterial spin labeling magnetic resonance imaging (pCASL MRI)'}], 'secondaryOutcomes': [{'measure': 'Bloodoxygen level-dependent (BOLD) functional MRI (fMRI) activity to measure appetite-related brain reward activity', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks', 'description': 'BOLD fMRI activity will be measured before and while participants watch food pictures'}, {'measure': 'Cognitive performance', 'timeFrame': 'From enrollment to the end of treatment at 24 weeks.', 'description': 'Cognitive performance measurement of the following cognitive domains: memory, executive function and psychomotor speed. Measurements will be performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB).'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Walnuts', 'Juglans', 'Brain vascular function', 'Brain insulin sensitivity', 'Satiety', 'Food reward mechanisms', 'Cognitive performance', 'Abdominal obesity', 'Cognitive decline', 'pCASL MRI', 'fMRI', 'CANTAB', 'Intranasal insulin', 'Food cues'], 'conditions': ['Healthy', 'Brain Insulin Sensitivity', 'Cerebral Blood Flow', 'Brain Vascular Function', 'Satiety and Food Intake', 'Food Reward', 'Cognitive Performance', 'Abdominal Obesity', 'Cognitive Decline']}, 'descriptionModule': {'briefSummary': 'Rationale: Healthy foods, including mixed nuts, may improve brain function, which is essential for cognitive and metabolic health, and may contribute to improved food intake regulation. It is therefore important to investigate the specific effects of walnuts on cerebral blood flow responses before and after intranasal insulin administration, as well as their associated functional benefits. The investigators hypothesize that long-term walnut consumption improves vascular function and insulin-sensitivity in the brain, thereby enhancing cognitive performance and appetite control in abdominally obese men and women. Objective: The primary objectives are to investigate in abdominally obese adults the effects of 24-week walnut consumption on (regional) vascular function and insulin-sensitivity in the brain, while the investigators will also assess changes in cognitive performance and appetite-related brain reward activity (secondary objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL). Study design: This intervention study will have a randomized, controlled parallel design. The total study duration will be 24 weeks. Study population: Fifty-five abdominally obese men and (postmenopausal) women (aged 45-75 years) without a history of cardiovascular diseases or complaints will participate. This study population is expected to have a decreased cerebral blood flow at baseline and are also at increased risk of cognitive impairment, allowing for improvement by the intervention. Intervention: Study participants will receive daily 50 g (about 15% of energy) of raw walnuts (walnut intervention) or no walnuts (control intervention) for 24 weeks. Main study parameters/endpoints: At baseline and after 24 weeks (follow-up), participants will visit the research facilities for assessments. The primary endpoint is the difference in the cerebral blood flow response before and after intranasal insulin administration between the walnut and control intervention. Cognitive performance will be assessed, while the investigators will also focus on appetite-related brain reward activity (secondary outcomes).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '45 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Men and women, aged between 45-75 years\n* Women postmenopausal: two or more years after last menstruation\n* Waist circumference of ≥102 cm for men and ≥88 cm for women (abdominal obesity)\n* Fasting plasma glucose \\< 7.0 mmol/L\n* Fasting serum total cholesterol \\< 8.0 mmol/L\n* Fasting serum triacylglycerol \\< 4.5 mmol/L\n* Systolic blood pressure \\< 160 mmHg and diastolic blood pressure \\< 100 mmHg\n* Stable body weight (weight gain or loss \\< 3 kg in the past three months)\n* 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\n* No difficult venipuncture as evidenced during the screening visit\n\nExclusion Criteria:\n\n* Allergy or intolerance to walnuts\n* Left-handedness (effects on brain function differ between left- and right-handed adults)\n* Current smoker, or smoking cessation \\< 12 months\n* Diabetic patients\n* Familial hypercholesterolemia\n* Abuse of drugs\n* More than 3 alcoholic consumptions per day\n* Use of products or dietary supplements (e.g., dietary fiber or antioxidant dietary supplements (vitamin C and E), fish or seaweed oil capsules) known to interfere with the main outcomes as judged by the principal investigators\n* Use of medication to treat blood pressure, lipid, or glucose metabolism\n* Use of an investigational product within another biomedical intervention trial within the previous 1-month\n* 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\n* Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident\n* Contra-indications for MRI imaging (e.g., pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)'}, 'identificationModule': {'nctId': 'NCT07422220', 'acronym': 'WalBrain', 'briefTitle': 'Long-Term Effects of Walnut Consumption on Brain Function', 'organization': {'class': 'OTHER', 'fullName': 'Maastricht University Medical Center'}, 'officialTitle': 'Long-Term Effects of Walnut Consumption on Brain Function in Men and Women With Abdominal Obesity', 'orgStudyIdInfo': {'id': 'METC 25-018'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Walnut', 'description': 'Receive 50g walnuts per day', 'interventionNames': ['Dietary Supplement: Walnuts']}, {'type': 'NO_INTERVENTION', 'label': 'Control', 'description': 'Does not receive walnuts and is supposed to refrain from nut consumption'}], 'interventions': [{'name': 'Walnuts', 'type': 'DIETARY_SUPPLEMENT', 'description': '24-week consumption of 50 g/day of walnuts as part of a healthy diet according to the Dutch dietary guidelines', 'armGroupLabels': ['Walnut']}]}, 'contactsLocationsModule': {'locations': [{'zip': '6200MD', 'city': 'Maastricht', 'state': 'Limburg', 'country': 'Netherlands', 'contacts': [{'name': 'Peter J. Joris, PhD', 'role': 'CONTACT', 'email': 'p.joris@maastrichtuniversity.nl', 'phone': '+31883887250'}, {'name': 'Linda J. Kehr, MSc', 'role': 'CONTACT', 'email': 'linda.kehr@maastrichtuniversity.nl', 'phone': '+31433883931'}, {'name': 'Peter J. Joris, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Maastricht University, Department of Nutrition and Movement Sciences', 'geoPoint': {'lat': 50.84833, 'lon': 5.68889}}], 'centralContacts': [{'name': 'Peter J. Joris, PhD', 'role': 'CONTACT', 'email': 'p.joris@maastrichtuniversity.nl', 'phone': '+31883887250'}, {'name': 'Linda J. Kehr, MSc', 'role': 'CONTACT', 'email': 'linda.kehr@maastrichtuniversity.nl', 'phone': '+31433883931'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Maastricht University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'California Walnut Commission', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}