Clinical trial NCT04286555: Dietary Approaches to Stop Hypertension for Diabetes
Official title: Dietary Approaches to Stop Hypertension for Diabetes Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Diabetes
Diabetes type2
Type2 Diabetes
Type 2 Diabetes
Type II Diabetes
Hypertension
High Blood Pressure
Keywords: diet
DASH
sodium
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Sheikh Khalifa Stroke Institute at Johns Hopkins
name: University of Colorado, Denver
First posted: 2020-02-27
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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 with diabetes 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: DASH4D Main Trial:

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 with diabetes 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 diets, presented in random order:

1. DASH4D diet with lower sodium
2. DASH4D diet with higher sodium
3. comparison diet with lower sodium
4. 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.

DASH4D CONTINUOUS GLUCOSE MONITORING (CGM) ANCILLARY STUDY:

Continuous glucose monitoring (CGM) systems are novel technologies recommended for assessing real-time glucose patterns, biochemical hypoglycemia, and glycemic variability. The DASH4D-CGM ancillary study will offer CGM to all participants in the DASH4D trial during a screening visit and during the two weeks at the end of each of four feeding periods.

CGM outcomes will be based on CGM data captured from week 3 to week 5 (up to 14 days) of each 5-week feeding period. Per current analytic recommendations, CGM outcomes will be generated using all available CGM data for each feeding period. The primary CGM outcomes are mean glucose, time-in-range (percentage of time glucose is between 70 and 180 mg/dL), and coefficient of variation. These outcomes were selected based on clinical guidelines and recommendations from a consensus statement on CGM endpoints for clinical trials.

We hypothesized that salt would have no effect on glucose. Therefore, we plan to combine data from the lower and higher sodium feeding periods for each diet to increase statistical power. Our primary aim is to examine the average difference in mean glucose, time-in-range, and coefficient of variation between the DASH4D and comparison diets.

Eligibility criteria: 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 Chronic Kidney Disease Epidemiology Collaboration (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

  1. 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
  2. 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)
  3. Unwillingness to keep same dose of vitamin, mineral, and botanical supplements
  4. 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

DASH4D-CGM ANCILLARY STUDY EXCLUSION CRITERIA:

All DASH4D main trial participants will be invited to participate in the embedded CGM ancillary study. Participants with the following contraindications to wearing a CGM sensor will be excluded from the ancillary study:

* History of allergic skin reaction to adhesive
* Implantable pacemaker

Note: Participants excluded from, or who do not wish to participate in, the CGM ancillary study are still allowed to participate in the DASH4D main trial if eligible.

Primary outcomes:
measure: Systolic blood pressure (SBP)
timeFrame: At the end of 5-week feeding period
Secondary outcomes:
measure: Diastolic blood pressure (DBP)
timeFrame: At the end of 5-week feeding period
Other outcomes:
measure: Glycated albumin level
timeFrame: At the end of 5-week feeding period
measure: Fructosamine level
timeFrame: At the end of 5-week feeding period
measure: Fasting glucose level
timeFrame: At the end of 5-week feeding period
measure: Hemoglobin A1c (HbA1c) level
timeFrame: At the end of 5-week feeding period
measure: Cardiovascular disease (CVD) risk percentage
timeFrame: At the end of 5-week feeding period
measure: Total cholesterol level
timeFrame: At the end of 5-week feeding period
measure: Low-density lipoprotein (LDL) cholesterol level
timeFrame: At the end of 5-week feeding period
measure: High-density lipoprotein (HDL) cholesterol level
timeFrame: At the end of 5-week feeding period
measure: Triglyceride level
timeFrame: At the end of 5-week feeding period
measure: Presence of orthostatic hypotension
timeFrame: At the end of 5-week feeding period
measure: Postural change in systolic blood pressure
timeFrame: At the end of 5-week feeding period
measure: Postural change in diastolic blood pressure
timeFrame: At the end of 5-week feeding period
measure: Symptoms experienced by participants as assessed by a questionnaire
timeFrame: At the end of 5-week feeding period
measure: Mean continuous glucose monitoring sensor glucose
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose between 70 and 180 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Glucose coefficient of variation (%)
timeFrame: At the end of 5-week feeding period
measure: Glucose standard deviation
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose above 180 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose above 250 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose below 70 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose below 54 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose between 70 to 140 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Percentage of time glucose above 140 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with >70% time glucose between 70 to 180 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with glucose coefficient of variation <36%
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with <25% time glucose above 180 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with <5% time glucose above 250 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with <4% time glucose below 70 mg/dL
timeFrame: At the end of 5-week feeding period
measure: Proportion of participants with <1% time glucose below 54 mg/dL
timeFrame: At the end of 5-week feeding period
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins ProHealth
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Lawrence Appel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Hsin Chieh Yeh, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Scott Pilla, MD, MHS
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Elizabeth Selvin, PhD
role: PRINCIPAL_INVESTIGATOR
References: