Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) Diet in Patients With Intracranial / Carotid Stenosis

Study Overview
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Brief Summary
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To test the effects of 6 month additional intervention of ORIENT diet versus usual medical treatment for Intracranial / Carotid Stenosis on cognitive decline, multi-mode MRI image markers and serum and fecal biomarkers in a randomized controlled trial of 120 patients with intracranial / carotid stenosis, who are aged older than 40 years and without dementia.

Detailed Description
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Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) diet in Patients With Intracranial / Carotid Stenosis is designed to test the impact of a 6-month intervention utilizing a culturally adapted version of the MIND diet, named as the ORIENT diet, on 120 older patients (aged 40 years and above and without dementia) diagnosed with intracranial/carotid stenosis (defined as ≥ 50% stenosis in unilateral intracranial/carotid artery as detected by vascular imaging diagnostic techniques, such as magnetic resonance angiography). The ORIENT diet retains the core components of the DASH, Mediterranean, and MIND diets, but incorporates adjustments according to evidence derived from Asian prospective cohorts and Chinese dietary practices. Participants in the intervention group will receive standard medical treatment in conjunction with the ORIENT diet intervention, while those in the control group will undergo standard medical treatment and receive usual dietary advice. The study's primary objective is to assess the influence of the ORIENT diet on cognitive function and brain macro- and microstructural integrity in patients with intracranial/carotid stenosis. This will be achieved through the administration of neuropsychological assessments and multi-modal magnetic resonance imaging at 6-month intervals until the completion of the trial. The investigation will explore potential mediators and modifiers of the intervention's effects by examining various cardiovascular risk factors, serum and fecal biomarkers, and underlying biological mechanisms.

Official Title
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Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) Diet in Patients With Intracranial / Carotid Stenosis : a Randomized Controlled Trial

Conditions
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Cognitive Decline, Cognitive Change, Stenosis, Dementia

Intervention / Treatment
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* Behavioral: Usual Diet advice
* Behavioral: Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 40 years ≥ 50% stenosis in unilateral intracranial / carotid artery Written informed consent available Willingness to complete all assessments and participate in follow-up Adequate Visual and auditory acuity to undergo neuropsychological testing Exclusion Criteria: Previous history of major head trauma and any intracranial surgery Intracranial abnormalities, such as intracerebral hemorrhage, subarachnoid hemorrhage and other space occupying lesions Extrapyramidal symptoms or mental illness which may affect neuropsychological measurement Severe loss of vision, hearing, or communicative ability Nuts, berries, olive oil, or fish allergies Patients presenting a malignant disease with life expectancy < 3 years Participation in an ongoing investigational drug study Exit Criteria: Not meet the inclusion criteria For any poor adherence, not comply with the requirements of the follow-up, or safety reasons determined by investigator Any adverse or serious adverse events during the study period judged by Investigator

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Usual Diet advice<br>Usual diet advice + standard medical treatment | Behavioral: Usual Diet advice<br>* The usual diet advice include recommendations in guidelines, such as reducing salt and limiting alcohol consumption<br>|
| Active Comparator: ORIENT diet intervention<br>6 month intervention of ORIENT diet + standard medical treatment | Behavioral: Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) diet<br>* The ORIENT diet has the same basic components of the Dietary Approaches to Stop Hypertension (DASH), Mediterranean and MIND diets, but uniquely adjusting some of components according to the evidence derived from Asian prospective cohorts and the Chinese eating habits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global cognitive function change assessed with Z-score of a modified National Institute of Neurological Disorders and Stroke and Canadian Stroke Network-Canadian Stroke Network (NINDS-CSN) protocol | Primary Outcome | 6 and 12 months; 2, 3 and 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive domain change assessed with NINDS-CSN protocol, including working memory, executive function, language, visual motor speed, visual spatial function, memory and recognition | short-term secondary outcome | 6 and 12 months | 
| Cognitive domain change assessed with NINDS-CSN protocol, including working memory, executive function, language, visual motor speed, visual spatial function, memory and recognition | long-term secondary outcome | 2,3 and 5 years | 
| Cognitive function change assessed with Mini-Mental State Examination (minimum value = 0, maximum value = 30, and higher scores mean a better outcome) | short-term secondary outcome | 6 and 12 months | 
| Cognitive function change assessed with Mini-Mental State Examination (minimum value = 0, maximum value = 30, and higher scores mean a better outcome) | long-term secondary outcome | 2,3 and 5 years | 
| Cognitive function change assessed by Montreal Cognitive Assessment (minimum value = 0, maximum value = 30, and higher scores mean a better outcome) | short-term secondary outcome | 6 and 12 months | 
| Cognitive function change assessed by Montreal Cognitive Assessment (minimum value = 0, maximum value = 30, and higher scores mean a better outcome) | long-term secondary outcome | 2,3 and 5 years | 
| Changes in functional network-related characteristics assessed by functional magnetic resonance imaging (fMRI), including intra- and inter-network connectivity, graph theory, and dynamic functional connectivity | short-term secondary outcome | 6 and 12 months | 
| Changes in functional network-related characteristics assessed by fMRI, including intra- and inter-network connectivity, graph theory, and dynamic functional connectivity | long-term secondary outcome | 2,3 and 5 years | 
| Changes in white matter hyperintensity (WMH) assessed on MRI with T2-Fluid-Attenuated-Inversion-Recovery (FLAIR) sequence | short-term secondary outcome | 6 and 12 months | 
| Changes in lacunes assessed on MRI with T2 FLAIR sequence | short-term secondary outcome | 6 and 12 months | 
| Changes in perivascular spaces assessed on MRI with T2 FLAIR sequence | short-term secondary outcome | 6 and 12 months | 
| Changes in microbleeds assessed on MRI with Susceptibility Weighted Imaging (SWI) sequence sequence | short-term secondary outcome | 6 and 12 months | 
| Changes in brain atrophy assessed on MRI | short-term secondary outcome | 6 and 12 months | 
| Changes in WMH assessed on MRI with T2 FLAIR sequence | long-term secondary outcome | 2,3 and 5 years | 
| Changes in lacunes assessed on MRI with T2 FLAIR sequence | long-term secondary outcome | 2,3 and 5 years | 
| Changes in perivascular spaces assessed on MRI with T2 FLAIR sequence | long-term secondary outcome | 2,3 and 5 years | 
| Changes in microbleeds assessed on MRI with SWI sequence sequence | long-term secondary outcome | 2,3 and 5 years | 
| Changes in brain atrophy assessed on MRI | long-term secondary outcome | 2,3 and 5 years | 
| Changes in cerebral glymphatic function assessed by non-invasive diffusion tensor image analysis along the perivascular space (ALPS-index) | short-term secondary outcome | 6 and 12 months | 
| Changes in cerebral glymphatic function assessed by non-invasive diffusion tensor image analysis along the perivascular space (ALPS-index) | long-term secondary outcome | 2,3 and 5 years | 
| Changes in cerebral blood flow (CBF) in the territory of the culprit artery assessed by arterial spin labeling (ASL) perfusion image | short-term secondary outcome | 6 and 12 months | 
| Changes in cerebral blood flow (CBF) in the territory of the culprit artery assessed by arterial spin labeling (ASL) perfusion image | long-term secondary outcome | 2,3 and 5 years | 
| Metabolite composition to measure the metabolite profiles in participants' faecal samples and serum samples | short-term secondary outcome: metabolite composition was analyzed via liquid chromatography tandem mass spectrometry (LC-MS/MS) | 6 months | 
| Metabolite composition to measure the metabolite profiles in participants' faecal samples and serum samples | long-term secondary outcome: metabolite composition was analyzed via liquid chromatography tandem mass spectrometry (LC-MS/MS) | 2 years | 
| Gut microbiota determined by measuring specific bacterial levels in the fecal samples | short-term secondary outcome | 6 months | 
| Gut microbiota determined by measuring specific bacterial levels in the fecal samples | long-term secondary outcome | 2 years | 
| Incidence of stroke event including ischemic and hemorrhagic stroke |  | 6 and 12 months; 2, 3 and 5 years | 
| Change in the Oriental Intervention for Enhanced Neurocognitive Health (ORIENT) diet scale (minimum value = 0, maximum value = 14, and higher scores mean a better outcome) | short-term secondary outcome | 6 months | 
| Change in the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet scale (minimum value = 0, maximum value = 15, and higher scores mean a better outcome). | short-term secondary outcome | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive decline