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| ID | Type | Description | Link |
|---|---|---|---|
| UL1TR001420 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
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Metabolic syndrome is considered to be a state of prediabetes and is a major risk factor for cardiovascular disease. Dietary interventions involving extra virgin olive oil (EVOO) supplementation and tree nut consumption can improve cardiometabolic health and reverse metabolic syndrome. The goal of this exploratory study is to establish the feasibility of using a novel measure - epigenetic age - to motivate behavior change and improve cardiometabolic health in individuals with metabolic syndrome.
Metabolic syndrome (MetS) is a collection of at least three out of five cardiometabolic risk factors including abdominal obesity, hypertension, elevated blood glucose, hypertriglyceridemia, and low high-density lipoprotein cholesterol. MetS is a major risk factor for cardiovascular disease and is considered a state of prediabetes. Improving metabolic parameters through dietary, behavioral, and pharmacological interventions can improve or reverse MetS. For example, increased consumption of extra virgin olive oil (EVOO) and mixed nuts was shown to reduce cardiovascular event rates and reverse MetS in a 5-year study in Spain (PREDIMED study). However, lower levels of adherence to the PREDIMED intervention was found in participants with a higher number of cardiovascular risk factors, larger waist circumference, and lower physical activity levels at baseline. New strategies to convey one's risk of morbidity and mortality at the onset of a dietary intervention may improve intervention adherence, particularly among individuals meeting the criteria for MetS.
A greater DNA methylation-based predicted age relative to chronological age, often referred to as "epigenetic age acceleration", has been associated with many lifestyle factors, including physical activity and diet, as well as components of MetS, including obesity, blood pressure, HDL cholesterol and blood glucose levels.
The investigators hypothesize that the majority of people with MetS have advanced epigenetic aging, and among those that have advanced epigenetic age, learning one's epigenetic age, and epigenetic age-based predicted risk of morbidity and mortality at the onset of a dietary intervention will improve participant adherence to the dietary intervention. Further, the investigators hypothesize that EVOO and tree nut supplementation in participants with MetS and advanced epigenetic age could help reverse MetS and potentially slow epigenetic aging. Therefore, the investigators plan to conduct a feasibility pilot study to:
For this study the investigators will recruit ~50 individuals with MetS aged 35 years or older. An in-person assessment visit will be scheduled for a morning time and participants will be asked to be fasting and will be instructed to bring their medications to the visit. Candidates will review the informed consent document at an in-person screening with study staff prior to beginning their participation. For all participants providing informed consent, who were fasting and met the MetS criteria at the initial in-person assessment visit, collected blood samples will be used to calculate epigenetic age acceleration. Other measures to be collected include body weight, height, waist circumference, blood pressure, and questionnaires about demographics, health history and health habits. Participants that meet the inclusion criteria during the in-person screening visit will be contacted to schedule a baseline intervention visit.
At the intervention visit, all participants will receive a 4-week supply of EVOO and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 10-day supply of each type). Participants will be asked to supplement their normal diets with these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. The investigators will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. Dietary adherence diaries will be given to measure incorporation of the study foods.
Participants will be randomized to learn about epigenetic age acceleration (arm 1) or not to learn about epigenetic age acceleration (arm 2) in a 1:1 allocation at the baseline visit. Those in the intervention arm 1 that are to learn about epigenetic age acceleration will receive some educational materials and a brief description of epigenetic age acceleration.
A telephone visit will be scheduled to take place at the end of week 1 for additional diet counseling, to assess safety/potential side effects and to collect adherence diaries. A follow-up phone call for compliance assessment and to answer participant questions will be conducted at the end of week 2. A final measurement visit will be scheduled for the end of week 4 for a morning time and participants will be asked to be fasting. At the final measurement visit, the same measures as listed in the in-person assessment visit will be performed and study questionnaires, with the exception of demographics and health history, will be distributed.
After the intervention, participants will be asked to come in for the end of week 4 visit, For participants in the intervention arm 1 (participants educated about epigenetic age acceleration), a self- administered exit questionnaire will be given to qualitatively explore participants' perception of epigenetic age, and challenges and motivators for behavior change during the intervention, The open-ended questions will be designed to ascertain understanding of epigenetic age, and assess the challenges and motivators participants encounter during the intervention.
Participants in both arms will be administered an Intervention Experience Assessment to explore how participant's experiences would impact the feasibility of a larger clinical intervention in terms of challenges and motivators.
This feasibility study, incorporating epigenetic age estimates with a dietary intervention in individuals with MetS, is an initial step in building our understanding of 1) the relationship between MetS and epigenetic age, 2) how epigenetic age estimates may be perceived by patients at high risk for CVD, and 3) will provide preliminary longitudinal data examining the potential to slow epigenetic age acceleration predictions after a 4-week dietary intervention to provide feasibility for a larger future study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epigenetic age knowledge arm | Active Comparator | Half of the intervention participants will be randomly selected to be informed of epigenetic age before the intervention. |
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| No epigenetic age knowledge arm | Active Comparator | The other half of intervention participants will not be informed of epigenetic age before the intervention. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daily consumption of tree nuts and extra virgin olive oil | Behavioral | All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants With MetS With Epigenetic Age Acceleration | To characterize the relationship between MetS and epigenetic aging, we will examine epigenetic age acceleration prevalence among the 50 participants with metabolic syndrome. | In-person 1 day assessment visit |
| Proportion of Days for Which EVOO Was Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which EVOO was taken | 4 weeks |
| Proportion of Days for Which Nuts Were Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which nuts were taken | 4 weeks |
| Proportion of Days for Which Nuts and EVOO Were Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which both nuts and of EVOO were taken | 4 weeks |
| Percentage of Participants Would be Able to Continue Eating the Tree Nuts and EVOO for a Study Like This Lasting 3-4 Years | Qualitative interview with open-ended questions designed to ascertain participant understanding of epigenetic age, and assess the challenges and motivators participants encountered during the intervention. Will be assessed using qualitative analysis methods. | After 4-week intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Epigenetic Age Acceleration | The investigators will compare epigenetic age acceleration before and after the 4-week intervention via DNA methylation test.DNA methylation profiles (beta-value, after adjustment chip and position effects) at 1,030 unique DNA methylation profiles will be used for epigenetic age acceleration predictions, using the DNA GrimAge predictor. The investigators will calculate predicted lifespan and regress predicted lifespan on chronological age to produce estimates of epigenetic age acceleration. |
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Inclusion Criteria:
Waist circumference >102 cm in men and >88cm in women, triglycerides >150 mg/dL and/or drug treatment for elevated triglycerides, HDL cholesterol <40 mg/dL in men and <50 mg/dL in women and/or drug treatment for reduced HDL cholesterol, systolic blood pressure >130 mm Hg or diastolic blood pressure >85 mmHg and/or antihypertensive drug treatment, and fasting glucose >100 mg/dL or hemoglobin A1c > 5.6% and/or oral hypoglycemic medications.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lindsay Reynolds, PhD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
There are no plans to make IPD available to other researchers
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| ID | Title | Description |
|---|---|---|
| FG000 | Epigenetic Age Knowledge Arm | Half of the intervention participants will be randomly selected to be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
| FG001 | No Epigenetic Age Knowledge Arm | The other half of intervention participants will not be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Epigenetic Age Knowledge Arm | Half of the intervention participants will be randomly selected to be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Participants With MetS With Epigenetic Age Acceleration | To characterize the relationship between MetS and epigenetic aging, we will examine epigenetic age acceleration prevalence among the 50 participants with metabolic syndrome. | 3 samples failed DNAm QC analyses - 1 sample failed QC analyses | Posted | Number | proportion of participants AgeAccelGrim> | In-person 1 day assessment visit |
|
Reporting time frame (ex. Baseline through 4 weeks): Intervention visit through final in person visit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Epigenetic Age Knowledge Arm | Half of the intervention participants will be randomly selected to be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Nausea | Systematic Assessment | Nausea |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lindsay Reynolds, PhD | Wake Forest University Health Sciences | 336.713.1134 | lireynol@wakehealth.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 14, 2022 | Aug 10, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 10, 2022 | May 2, 2022 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D024821 | Metabolic Syndrome |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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Knowledge of intervention arm will not be given to research labs with samples
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| In-person 1 day assessment visit vs. final 1 day visit after 4-week intervention |
| BG001 | No Epigenetic Age Knowledge Arm | The other half of intervention participants will not be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | No Epigenetic Age Knowledge Arm | The other half of intervention participants will not be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. |
|
|
| Primary | Proportion of Days for Which EVOO Was Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which EVOO was taken | 3 samples failed DNAm QC analyses - 1 sample failed QC analyses | Posted | Mean | Standard Deviation | proportion of days | 4 weeks |
|
|
|
| Primary | Proportion of Days for Which Nuts Were Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which nuts were taken | 3 samples failed DNAm QC analyses - 1 sample failed QC analyses | Posted | Mean | Standard Deviation | proportion of days | 4 weeks |
|
|
|
| Primary | Proportion of Days for Which Nuts and EVOO Were Taken | Adherence for each participant will be measured as the proportion of days in 4 weeks for which both nuts and of EVOO were taken | 3 samples failed to generate DNAm data passing QC analyses 1 sample failed to generate DNAm data passing QC analyses | Posted | Mean | Standard Deviation | proportion of days | 4 weeks |
|
|
|
| Primary | Percentage of Participants Would be Able to Continue Eating the Tree Nuts and EVOO for a Study Like This Lasting 3-4 Years | Qualitative interview with open-ended questions designed to ascertain participant understanding of epigenetic age, and assess the challenges and motivators participants encountered during the intervention. Will be assessed using qualitative analysis methods. | % that would be able to continue eating the tree nuts and EVOO for a study like this lasting 3-4 years | Posted | Number | Percentage of Participants | After 4-week intervention |
|
|
|
| Secondary | Changes in Epigenetic Age Acceleration | The investigators will compare epigenetic age acceleration before and after the 4-week intervention via DNA methylation test.DNA methylation profiles (beta-value, after adjustment chip and position effects) at 1,030 unique DNA methylation profiles will be used for epigenetic age acceleration predictions, using the DNA GrimAge predictor. The investigators will calculate predicted lifespan and regress predicted lifespan on chronological age to produce estimates of epigenetic age acceleration. | 3 samples failed to generate DNAm data passing QC analyses - 1 sample failed to generate DNAm data passing QC analyses | Posted | Mean | Standard Deviation | AgeAccelGrim (years) | In-person 1 day assessment visit vs. final 1 day visit after 4-week intervention |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 2 |
| 17 |
| EG001 | No Epigenetic Age Knowledge Arm | The other half of intervention participants will not be informed of epigenetic age before the intervention. Daily consumption of tree nuts and extra virgin olive oil: All participants will receive a 4-week supply of extra virgin olive oil and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 3-day supply of each type). Participants will be asked to include in their normal diets these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. We will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. | 0 | 17 | 0 | 17 | 3 | 17 |
| Hyperglycemia | Blood and lymphatic system disorders | Hyperglycemia | Systematic Assessment | Hyperglycemia |
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| Pruritus | Infections and infestations | Pruritus | Systematic Assessment | Pruritus |
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| Hypotension | Vascular disorders | Hypotension | Systematic Assessment | Hypotension |
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| Weight Gain | Endocrine disorders | Weight Gain | Systematic Assessment | Weight Gain |
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| Indigestion | Gastrointestinal disorders | Indigestion | Systematic Assessment | Indigestion |
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| Upset Stomach | Gastrointestinal disorders | Upset Stomach | Systematic Assessment | Upset Stomach |
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| bloating or increased bloating | Gastrointestinal disorders | bloating or increase | Systematic Assessment | bloating or increased bloating |
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| Increased stool frequency | Gastrointestinal disorders | Increased stool freq | Systematic Assessment | Increased stool frequency |
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| Loose Bowel movement | Metabolism and nutrition disorders | Loose Bowel movement | Systematic Assessment | Loose Bowel movement |
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| Gas/Belching | Gastrointestinal disorders | Gas/Belching | Systematic Assessment | Gas/Belching |
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| Stye in eye | Eye disorders | Stye in eye | Systematic Assessment | Stye in eye |
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| Sinus HA with nose bleed | Skin and subcutaneous tissue disorders | Sinus HA with nose b | Systematic Assessment | Sinus HA with nose bleed |
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| Stomach bug with diarrhea | Gastrointestinal disorders | Stomach bug with dia | Systematic Assessment | Stomach bug with diarrhea |
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| Worsening knee pain and inflammation | Musculoskeletal and connective tissue disorders | Worsening knee pain | Systematic Assessment | Worsening knee pain and inflammation |
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| Lips raw on inside | Skin and subcutaneous tissue disorders | Lips raw on inside | Systematic Assessment | Lips raw on inside |
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| Carpal tunnel | Musculoskeletal and connective tissue disorders | Carpal tunnel | Systematic Assessment | Carpal tunnel |
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| Decreased frequency of bowel movements | Gastrointestinal disorders | Decreased frequency | Systematic Assessment | Decreased frequency of bowel movements |
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| Explosive bowel movement) | Gastrointestinal disorders | Explosive bowel move | Systematic Assessment | Explosive bowel movement) |
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| Fatigue | Metabolism and nutrition disorders | Fatigue | Systematic Assessment | Fatigue |
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| Infection- Leg sore | Infections and infestations | Infection- Leg sore | Systematic Assessment | Infection- Leg sore |
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| Vomiting | Gastrointestinal disorders | Vomiting | Systematic Assessment | Vomiting |
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| Acid reflux/ increased acid reflux | Gastrointestinal disorders | Acid reflux/ increas | Systematic Assessment | Acid reflux/ increased acid reflux |
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| Constipation | Gastrointestinal disorders | Constipation | Systematic Assessment | Constipation |
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| D009750 |
| Nutritional and Metabolic Diseases |