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Approximately 30% of patients experience "Long-COVID" syndrome presenting with symptoms such as cognitive difficulties ('brain fog'), fatigue, dyspnea, autonomic dysfunction, depression and anxiety, lasting beyond 12 weeks causing significant disability, and threaten health and wellbeing of millions around the world. At the current time, there is no effective treatment for long-COVID. Walnuts contain a mixture of nutrients and phytochemicals include monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and alpha-linolenic acid (ALA). Walnut consumption was directly associated with cognitive function. The investigators have shown pomegranate that share the same phytonutrient ellagitannins as walnut and mixed nuts including walnuts could increase blood microbiome metabolites of tryptophan metabolite indole propionate and serotonin levels via change of gut microbiota and therefore play an essential role in gut-brain axis including cognitive function. The proposed pilot study will include 76 adults (ages >40 years) with diagnosis of SARS-CoV2 infection presenting with long-COVID symptoms lasting longer than 12 weeks. They will be randomized 1:1 to usual care vs. an intervention group that will include 2 oz (57g) of walnuts daily into their habitual diet for 12 weeks. The investigators will compare the improvement in symptoms of cognitive complains of "brain fog", fatigue and depression of the active intervention group vs. usual care. The outcome of the investigation of the benefit of walnut consumption will provide important novel information on using dietary sources of polyunsaturated fatty acids and phytochemicals to mitigate the common symptoms of long-COVID. This application was submitted in response to the California Walnut Commission's commodity board topic.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Walnuts | Experimental |
| |
| Control | No Intervention | Habitual diet while avoiding nuts |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| whole food - walnuts | Other | Participants randomized to the intervention group will consume (2 oz ) of whole walnuts daily, incorporated into their diet for 12 weeks. Walnuts were provided to participants, and adherence was monitored using dietary records. |
| Measure | Description | Time Frame |
|---|---|---|
| Episodic Memory - RAVLT-Revised Long-Delay Free Recall (number of words recalled) | Change in long-delay free recall score (number of words correctly recalled) on the RAVLT-Revised from baseline to week 12. | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Executive Function | Digit Vigilance Test Score Description: Total completion time (seconds) and/or number of errors on the Digit Vigilance Test, assessing sustained attention and processing speed. | Baseline to Week 12 |
| Trail Making Test Part A Completion Time |
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Inclusion Criteria:
Age 40 years and older
History of confirmed SARS-CoV-2 infection
Presence of long-COVID symptoms lasting longer than 12 weeks, including one or more of the following:
Consumption of a low-polyphenol (Western) diet
Adequate visual acuity and hearing to complete neuropsychological testing
Screening laboratory results without clinically significant abnormalities that would interfere with study participation
Ability and willingness to provide written informed consent
Exclusion Criteria:
Diagnosis of probable Alzheimer's disease or other dementia (e.g., vascular, Lewy body, frontotemporal)
Other neurological or medical conditions that may cause cognitive impairment
Evidence of Parkinson's disease based on motor examination
Uncontrolled hypertension (systolic BP >170 mmHg or diastolic BP >100 mmHg)
Allergy to walnuts
Regular consumption of more than 5 oz of walnuts per week
Current diagnosis of a major psychiatric disorder according to DSM-5 criteria
Alcoholism or substance use disorder
Any condition that, in the investigator's judgment, would make participation unsafe or interfere with study completion
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Center for Human Nutrition | Los Angeles | California | 90025 | United States |
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| ID | Term |
|---|---|
| D000094024 | Post-Acute COVID-19 Syndrome |
| D005222 | Mental Fatigue |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
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Description: Time to completion (seconds) for Trail Making Test Part A, assessing processing speed. |
| baseline and 12 weeks |
| Fatigue | Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form - 8 Item. Fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form (8 items). Raw scores range from 8 to 40, with higher scores indicating greater fatigue (worse outcome). Scores may also be converted to standardized T-scores (mean = 50, SD = 10), where higher T-scores indicate greater fatigue. | Baseline and 12 |
| Mood | PROMIS® Depression Short Form (8 items) | baseline and 12 weeks |
| NIH Toolbox Cognitive Battery (NIHTB-CB) - Fluid Intelligence Composite | Fluid cognitive function will be assessed using the Fluid Intelligence Composite score from the NIH Toolbox Cognitive Battery. The composite is a standardized score (mean = 100, SD = 15), with higher scores indicating better cognitive performance. | Baseline to Week 12 |
| Quality of Life | SF-36 Health Survey | Baseline and 12 |
| Blood Pressure | Seated systolic and diastolic blood pressure Systolic and diastolic blood pressure will be measured in millimeters of mercury (mmHg) using an automated calibrated sphygmomanometer after 5 minutes of seated rest. Higher values indicate higher blood pressure. | Baseline and Week 12 |
| Dietary Intake | 24-hour dietary recall (ASA24™) | Baseline and 12 |
| Blood and Urine Biomarkers | Measures: metabolic markers and inflammatory Blood fatty acid profile Plasma ellagic acid Urinary urolithin metabolites (LC-MS/MS) | Baseline, 12 Weeks |
| WAIS-IV Symbol Search Score | Total correct responses (scaled score) on the WAIS-IV Symbol Search subtest, assessing processing speed. | Baseline and 12 weeks |
| Heart Rate | Resting heart rate Description: Resting heart rate will be measured in beats per minute (bpm) using an automated blood pressure monitor after 5 minutes of seated rest. | Baseline and Week 12 |
| Body Weight | Measure: Body weight in kilograms Description: Body weight will be measured in kilograms (kg) using a calibrated digital scale with participants wearing light clothing and no shoes. | baseline and week 12 |
| D007239 |
| Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005221 | Fatigue |
| D012816 | Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |