Dietary Approaches to Stop Hypertension for Diabetes

Study Overview
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Brief Summary
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The objective of the DASH4D trial is to determine the effects, alone and combined, of (a) the DASH4D diet (a DASH-style diet modified for people with diabetes) vs. comparison diet that is typical of what many Americans eat and (b) lower sodium intake vs. higher sodium intake on blood pressure (BP). The core design is a single-site, 4-period, crossover feeding study with 5-week periods. Participants are fed each of four isocaloric diets, presented in random order. The primary contrast of interest is DASH4D diet with lower sodium vs. comparison diet with higher sodium.

Detailed Description
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In persons with and without diabetes, elevated blood pressure (BP) is the leading cause of stroke and a major risk factor for other cardiovascular diseases, including coronary heart disease and heart failure. Strategies that effectively lower BP include drug therapy and lifestyle modification. Lifestyle modifications, particularly dietary approaches, have been shown to lower BP in persons without diabetes. However, there is a striking dearth of evidence on BP-lowering, lifestyle modifications, other than weight loss, in persons with diabetes. The DASH4D trial is designed to provide this evidence. The DASH4D trial builds upon the investigators' experience in four NIH-sponsored feeding studies (DASH, DASH-Sodium, OmniHeart, and OmniCarb). The trial will enroll approximately 100 adults with Type 2 diabetes, systolic BP 120-159 mmHg, and diastolic BP <100 mmHg, to determine the effects, alone and combined, of (a) the DASH4D diet (a DASH-style diet modified for people with diabetes) vs. comparison diet (typical of what many Americans eat) and (b) lower sodium intake vs. higher sodium intake on BP. The core design is a four-period, single-site, crossover feeding study with 5-week periods. Participants are fed each of four isocaloric diets, presented in random order: DASH4D diet with lower sodium DASH4D diet with higher sodium comparison diet with lower sodium comparison diet with higher sodium. The primary contrast of interest is the DASH4D diet with lower sodium vs. the comparison diet with higher sodium. The DASH4D diet is similar to the original DASH diet, but is lower in carbohydrates and higher in unsaturated fat than the original DASH diet, and therefore, is more consistent with dietary recommendations for persons with diabetes than the original DASH diet. The comparison diet reflects what many persons with diabetes currently consume. The lower sodium intake of approximately 1500 mg/day (at 2000 kcal) has been shown to lower BP in persons without diabetes, and has been recommended in some dietary guidelines. The higher sodium intake of approximately 3700 mg/day (at 2000 kcal) is based on estimated average intake in the US. Outcomes are measured at the end of each feeding period. The primary outcome is end-of-period, office-based systolic BP. Other outcomes are diastolic BP, measures of glycemia, plasma lipid risk factors, patient symptoms, and estimated cardiovascular disease risk. Similar to the investigators' prior feeding studies, the investigators expect that the results of the DASH4D trial will be immediately applicable to public health and clinical guidelines and will influence nutrition policy. Furthermore, the trial will provide a rigorous platform to assess the impact of diet and sodium intake on a diverse array of other outcomes in persons with Type 2 diabetes.

Official Title
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Dietary Approaches to Stop Hypertension for Diabetes Trial

Conditions
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Diabetes Mellitus, Type 2, Diabetes, Diabetes type2, Type2 Diabetes, Type 2 Diabetes, Type II Diabetes, Hypertension, High Blood Pressure

Intervention / Treatment
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* Other: DASH4D diet
* Other: comparison diet
* Other: higher sodium
* Other: lower sodium


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Age 18 or older Diabetes Mellitus Type 2 defined by HbA1c ≥6.5% or treatment of diabetes with diabetes medication(s) Baseline systolic BP of 120-159 mmHg (based on average across 3 screening visits) Baseline diastolic BP <100 mmHg (based on average across 3 screening visits) Willing and able to eat on site for one meal per day, 3 days per week, and eat only and all food provided as part of the study diets during the controlled feeding periods (run-in and four 5-week feeding periods). Note that actual frequency of on-site dining may be fewer than 3 days per week due to COVID-related restrictions, but participants will still need to be on site to pick up food and be weighed 3 days per week, and will still be expected to have meals monitored (in-person or remotely) for one meal per day, 3 days per week. Willing and able to complete required measurement procedures Have access to a mobile device or computer with video conference capabilities, or be willing to use a device for video conferencing provided by the study EXCLUSION CRITERIA: Laboratory Exclusions Serum potassium ≥5.2 mmol/L or <3.5 mmol/L Estimated glomerular filtration rate (eGFR) <30 mL/min by commercial lab result (note that prior to 7/12/22, the lab was using the race-based CKD Epi equation, and on/after 7/12/22, the lab switched to using the CKD-Epi 2021 equation, which does not provide different estimated GFR by race) HbA1c>9.0% Medication Exclusions Unstable dose (i.e., change in the 2 months prior to screening or prior to randomization) of any of the following: Anti-hypertensive medications Sodium-glucose co-transporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists Stimulants, including oral medications for asthma or chronic obstructive pulmonary disease (COPD) Hormone replacement therapy or thyroid hormone Weight-increasing psychotropic agents, including antipsychotic agents, lithium, and mirtazapine Use of any of the following medications: Potassium supplementation in any form, including a multivitamin or electrolyte drink mix, with a dose >99 mg/day, which is the allowable amount in over-the-counter products Prandial or short-acting insulin GLP-1 receptor agonist if on weight loss dose Warfarin (Coumadin) Chronic oral corticosteroid (intermittent use is okay) Weight loss medications Tirzepatide (Mounjaro) Unwillingness to keep same dose of vitamin, mineral, and botanical supplements Any medication not compatible with participation as determined by the investigators Medical History Exclusions Type 1 diabetes Hypoglycemia requiring hospitalization or the assistance of another person in the last 12 months Active cardiovascular disease or any event in the prior 6 months, including coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), myocardial infarction (MI), cerebrovascular accident (CVA), or congestive heart failure (CHF) exacerbation requiring hospital admission Cancer diagnosis or treatment in the last 2 years (benign tumors or non-melanoma skin cancer or localized breast or prostate cancer not requiring chemotherapy is acceptable) Active inflammatory bowel disease, bowel resection, malabsorptive syndrome, pancreatitis (episode within past year), history of Roux-en-Y gastric bypass, or history of other bariatric surgery that limits food intake volume or that requires a specific diet plan Pregnancy or lactation or planned pregnancy Any emergency department (ED) visit for asthma or chronic obstructive pulmonary disease (COPD) in the last 6 months Any other serious illness or condition not compatible with participation as determined by the investigators Physical Exclusions Body weight >420 pounds Arm circumference ≥50cm Weight loss or gain of >5.0% of body weight during 2 months prior to screening, or large weight change during screening prior to randomization Lifestyle and Other Exclusions Significant food allergies, preferences, intolerances, or dietary requirements that would interfere with diet adherence Not able to self-monitor glucose if needed Consumption of more than 14 alcoholic drinks per week or consumption of more than 6 drinks on one or more occasion per week Active substance use disorder that would interfere with participation Participation in or planning to start weight loss program Current participation in another clinical trial that might affect blood pressure or ability to comply with study procedures Planning to leave area prior to end of study Investigator discretion

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study design is a four-period crossover feeding study, in which participants will be randomly assigned to an order of four isocaloric diets for a 5-week period each.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DASH4D diet with lower sodium<br>DASH-style dietary pattern, modified for people with diabetes, with sodium level of 1500 mg/day | Other: DASH4D diet<br>* DASH stands for Dietary Approaches to Stop Hypertension. The DASH diet is a healthy dieter that lowers blood pressure. The DASH diet emphasizes fruits, vegetables, and low-fat dairy products; includes whole grains, poultry, fish, and nuts; and is reduced in red meat, sweets, and sugar-containing beverages. The DASH4D dietary pattern is a version of the DASH diet that is lower in carbohydrate.<br>Other: lower sodium<br>* 1500 mg/day sodium<br>|
| Active Comparator: DASH4D diet with higher sodium<br>DASH-style dietary pattern, modified for people with diabetes, with sodium level of 3700 mg/day | Other: DASH4D diet<br>* DASH stands for Dietary Approaches to Stop Hypertension. The DASH diet is a healthy dieter that lowers blood pressure. The DASH diet emphasizes fruits, vegetables, and low-fat dairy products; includes whole grains, poultry, fish, and nuts; and is reduced in red meat, sweets, and sugar-containing beverages. The DASH4D dietary pattern is a version of the DASH diet that is lower in carbohydrate.<br>Other: higher sodium<br>* 3700 mg/day sodium<br>|
| Active Comparator: Comparison diet with lower sodium<br>Dietary pattern that is typical of what many Americans eat, with sodium level of 1500 mg/day | Other: comparison diet<br>* The comparison dietary pattern is based on a typical American diet, with macronutrient distributions generally at the average of typical US intake, and micronutrient targets generally near the 25th percentile of usual US intake (with the exception of sodium).<br>Other: lower sodium<br>* 1500 mg/day sodium<br>|
| Other: Comparison diet with higher sodium<br>Dietary pattern that is typical of what many Americans eat, with sodium level of 3700 mg/day | Other: comparison diet<br>* The comparison dietary pattern is based on a typical American diet, with macronutrient distributions generally at the average of typical US intake, and micronutrient targets generally near the 25th percentile of usual US intake (with the exception of sodium).<br>Other: higher sodium<br>* 3700 mg/day sodium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure (SBP) | After the participant has rested quietly in the seated position for at least 5 minutes, blood pressure will be measured in triplicate, using an Omron device, with each reading separated by 30 seconds, and the average of the three readings (in mmHg) will also be recorded. Blood pressure will be measured on five separate occasions during the last 2 weeks of the feeding period, and the mean systolic blood pressure from these five blood pressures (15 total readings) will be used as the primary outcome. | At the end of 5-week feeding period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic blood pressure (DBP) | After the participant has rested quietly in the seated position for at least 5 minutes, blood pressure will be measured in triplicate, using an Omron device, with each reading separated by 30 seconds, and the average of the three readings (in mmHg) will also be recorded. Blood pressure will be measured on five separate occasions during the last 2 weeks of the feeding period, and the mean diastolic blood pressure from these five blood pressures (15 total readings) will be used as a secondary outcome. | At the end of 5-week feeding period | 
| Glycated albumin level | Glycated albumin percentage (%). | At the end of 5-week feeding period | 
| Fructosamine level | Fructosamine level in mmol/L. | At the end of 5-week feeding period | 
| Fasting glucose level | Fasting glucose level in mg/dL. | At the end of 5-week feeding period | 
| Hemoglobin A1c (HbA1c) level | HbA1c percentage (%). | At the end of 5-week feeding period | 
| Cardiovascular disease (CVD) risk percentage | Current 10-year atherosclerotic cardiovascular disease (ASCVD) risk will be reported as a percent, using the American College of Cardiology (ACC)/American Heart Association (AHA) ASCVD risk equation. | At the end of 5-week feeding period | 
| Total cholesterol level | Total cholesterol level in mg/dL. | At the end of 5-week feeding period | 
| Low-density lipoprotein (LDL) cholesterol level | LDL cholesterol level in mg/dL. | At the end of 5-week feeding period | 
| High-density lipoprotein (HDL) cholesterol level | HDL cholesterol level in mg/dL. | At the end of 5-week feeding period | 
| Triglyceride level | Triglyceride level in mg/dL. | At the end of 5-week feeding period | 
| Presence of orthostatic hypotension | Participants will lie in the supine position for 5 minutes and undergo three blood pressure measurements, separated by 30 seconds. The average of these three readings will be used as the supine blood pressure. They will stand with their arm rested on an adjacent Mayo table at 70-80 degrees from their torso, and they will then undergo another set of triplicate blood pressure measurements, separated by 30 seconds each. The average of these three readings will be used as the standing blood pressure. Presence of orthostatic hypotension will be defined as ≥ 20 mmHg drop in systolic blood pressure or a ≥ 10 mmHg drop in diastolic blood pressure upon standing. | At the end of 5-week feeding period | 
| Postural change in systolic blood pressure | Participants will lie in the supine position for 5 minutes and undergo three blood pressure measurements, separated by 30 seconds. The average of these three readings will be used as the supine blood pressure. They will stand with their arm rested on an adjacent Mayo table at 70-80 degrees from their torso, and they will then undergo another set of triplicate blood pressure measurements, separated by 30 seconds each. The average of these three readings will be used as the standing blood pressure. Change in systolic blood pressure (mmHg) upon standing will be calculated. | At the end of 5-week feeding period | 
| Postural change in diastolic blood pressure | Participants will lie in the supine position for 5 minutes and undergo three blood pressure measurements, separated by 30 seconds. The average of these three readings will be used as the supine blood pressure. They will stand with their arm rested on an adjacent Mayo table at 70-80 degrees from their torso, and they will then undergo another set of triplicate blood pressure measurements, separated by 30 seconds each. The average of these three readings will be used as the standing blood pressure. Change in diastolic blood pressure (mmHg) upon standing will be calculated. | At the end of 5-week feeding period | 
| Symptoms experienced by participants as assessed by a questionnaire | Participants will complete a questionnaire about symptoms experienced while on each diet, including symptoms related to fall risk (e.g., feeling faint), food intake and output (e.g., bloating, constipation), fluid intake and output (e.g., excessive thirst), and general symptoms (e.g., fatigue or low energy). Participants will be asked to rate each listed symptom as: did not occur, mild, moderate, or severe. | At the end of 5-week feeding period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diet, DASH, sodium