Clinical trial NCT03980574: Dietary Supplementation in Heart Failure
Official title: Dietary Supplementation in Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Diabetes Mellitus
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: Vascular Scientific, LLC
First posted: 2019-06-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2 arms of studying with first arm involving a cross-over from active intervention to no intervention and a second arm involving active intervention with no cross-over.
Primary purpose: TREATMENT

Brief summary: A single-center, double-blind, placebo-controlled, cross-over study pilot study comparing R Drink vs. placebo in 60 heart failure patients. Half of the participants will also have diabetes mellitus. The 60 patients will be distributed among three arms. Total distance walked in six minutes and hospital readmission rates will be examined. Eligible heart failure patients include those with systolic or diastolic heart failure and diabetes mellitus can be Type I or II. All patients will continue on their standard heart failure and diabetes therapies while they participate in the study.

Detailed description: Heart failure (HF) affects millions of Americans, with approximately five-hundred thousand new cases diagnosed annually, with 40% or more of patients having a concomitant diagnosis of diabetes or prediabetes. HF is not a diagnosis itself, but rather a constellation of signs and symptoms due to impaired ventricular filling or ejection of blood. Some of the most common symptoms associated with heart failure include dyspnea, impaired exercise tolerance, and lower extremity edema. Certain co-morbidities like hypertension (HTN) and DM are found more commonly in conjunction with HF. In fact, diabetes is an independent predictor of heart failure. Patients with heart failure and diabetes can have additional clinical symptoms of peripheral neuropathy and poor wound healing, often leading to foot ulcers. The mainstay of treatment for HF at present, employs the use of goal directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT).

Despite these treatments, HF still accounts for over 20% of all hospital admissions in people older than 65. The estimated cost for HF admissions in the US is over $35 billion.

In limited case study, testing participants with a variety of chronic diseases, including HF and DM, observations suggest the incorporation of a dietary supplement drink (R Drink) containing filtered reverse osmosis water and 150 mg/L of both USP Grade calcium chloride and magnesium chloride, 10 mg/L Biotin (vitamin B7), 500 mg/L of Niacinamide (B3) and 550 mg/L of Choline may be beneficial, which is the goal of this unique three-arm clinical trial.

These ingredients are Generally Recognized as Safe (GRAS) ingredients by the FDA and have multiple proposed mechanisms of action which include improved circulation and enhancing clearance of metabolic waste. These electronutrients play a role in the regulation of acetylcholine induced endothelium-dependent relaxation and regulation of nitric oxide, directly influencing vascular tone. They are involved in the s-adenosylmethionine and myelin pathways of the central nervous system, and promote the repair and protection of myelin which is essential for nerve conduction. These electronutrients may promote activation of adenosine triphosphate (ATP) which improves muscular contractions and nerve-muscle impulse transmission. Finally, by regulating the release of serum free fatty acid release, these specific electronutrients may assist in insulin regulation.

This pilot study will be a single center, double-blind, placebo controlled, cross-over study having three arms with a total of 60 patients - all with HF and half with DM - and will compare R Drink versus placebo on the distance walked in 6 minutes, and hospital readmission rates. Eligible patients will have a known diagnosis of HF (diastolic - HFpEF or systolic - HFrEF) classified as NYHA I-IV, a known diagnosis of DM (type I or type II) and will be selected from a larger population being followed in the Heart Failure Clinic at the Ohio State University Wexner Medical Center. All patients will continue on the standard HF and DM therapies as guided by their treating physician. Enrolled patients will be randomly assigned (2:1) to a crossover group (40 patients) and a non-crossover group (20 patients). The crossover group will be further randomly assigned (1:1) with 20 patients in each group. The two crossover arms of the study will follow the patients for 8 weeks. At the end of week 8, all crossover patients will have a 1 week wash out period. Thereafter, patients will be crossed-over to the opposing arm of the study for an additional 1+8 weeks (R Drink 8 oz 3-5x/day versus a placebo drink 8 oz 3-5x/day).

The third arm of the study will follow 20 patients for the entire 17 weeks and participants in this arm will not be crossed over, will not have a washout period, and will consume R Drink for the total duration of the study. If patients in this arm wish to continue on the R Drink, for 6 additional months they may do so. At the end of the optional 6 months these patients will have a repeat research transthoracic echocardiogram. Data collection will occur at baseline, week 8, and week 17. An additional 6 month data collection time point will occur for patients in the third arm opting to continue R Drink.

At the end of study participation, all patients in the two arms that cross will have the study drink discontinued and will continue to follow standard heart failure and diabetic therapies as guided by their treating physicians. The study will use a permuted block randomization. This design should result in a balance of known and unknown con-founders and prevent identification of the randomization sequence, minimizing potential selection bias due to investigator preference. The groups should have the same baseline characteristics and be evenly distributed. Each of the 20 patient cohorts should enroll 10 patients with diabetes within each cohort.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Confirmed diagnosis of heart failure (NYHA Class I-IV) (all subjects)
* Confirmed diagnosis of diabetes (type I or II) (only 30 subjects)
* At least 3 months of standard, conventional drug therapy for heart failure, including diuretic dosing. Diuretics can be adjusted during the study per the treating physician within a relatively standard dosing scale. Overall medical therapy should be considered maximally tolerated appropriate therapy by the treating physician.
* Ability to participate in 6-minute walk test
* Literacy and ability to complete neuropathic pain and heart failure quality of life questionnaires
* Signed written consent

Exclusion Criteria:

* Contraindications to the consumption of 1L of purified water per day, when taken into consideration that the average patient with HF is recommended to adhere to a 1.5-2 L fluid restriction per day
* Liver cirrhosis / Prior diagnosis of liver failure
* End-stage renal disease requiring hemo/peritoneal dialysis
* CHF admission requiring diuresis within 14 days prior to enrollment date
* Systolic BP \< 100 mmHg or diastolic BP \< 60 mmHg (at time of randomization)
* Blood glucose \< 70 mg/dl (at time of randomization)
* QRS duration \> 130 ms
* QTc duration \> 480 ms
* Prior diagnosis of moderate to severe COPD
* Uncontrolled systemic systolic/diastolic hypertension (SBP \> 160 mmHg or DBP \> 100 mmHg)
* Pregnancy
* History of ventricular tachycardia or SCD
* Refusal to consent/inability to provide signed written consent
* Any condition or abnormality that, at the physician's discretion, would compromise subject safety or data integrity

Primary outcomes:
measure: Hospital Readmission Rates
timeFrame: Day 119
Secondary outcomes:
Other outcomes:
measure: New York Heart Association Functional Class
timeFrame: Day 0, Day 119
measure: Echocardiographic Measurements
timeFrame: Day 0, Day 56, Day 119
measure: Quality of Life Questionnaires
timeFrame: Day 0, Day 56, Day 119
measure: 6-Minute Walk Test
timeFrame: Day 0, Day 56, and Day 119
measure: Serological Assessment
timeFrame: Day 0, Day 56, and Day 119
measure: Serological Assessment
timeFrame: Day 0, Day 56, and Day 119
measure: Serological Assessment
timeFrame: Day 0, Day 56, and Day 119
measure: Serological Assessment
timeFrame: Day 0, Day 56, and Day 119
measure: Serological Assessment
timeFrame: Day 0, and Day 119
Locations:
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Sitaramesh Emani, MD
role: PRINCIPAL_INVESTIGATOR
References: