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CompletedNCT00939640DASH-DHFUpdated Oct 15, 2019Results posted

Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet in Diastolic Heart Failure

An interventional study of DASH/sodium-restricted diet (SRD) in Diastolic Heart Failure and Hypertensive Heart Disease, sponsored by University of Michigan. Completed at 1 site in United States. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2019-10-15.

Sponsored by University of Michigan · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
14
Allocation
Not applicable
Ages
50 Years and older
Sex
All
01

Study summary

Heart failure with preserved systolic function (HF-PSF, or 'diastolic heart failure') accounts for half of hospitalizations for heart failure in patients over the age of 65. Most HF-PSF patients have systemic hypertension (HTN), and characteristic HTN-induced cardiovascular changes contribute to HF-PSF. However, it is unclear why most patients with HTN never develop HF-PSF or which specific aspects of HTN predispose to HF-PSF.

In the Dahl S rat, the primary animal model of HF-PSF, high dietary sodium intake suppresses the systemic renin-angiotensin-aldosterone system, but upregulates renal and cardiac renin-angiotensin-aldosterone system by inducing oxidative stress. In humans, the magnitude of blood pressure response to sodium ingestion and depletion can categorize subjects as "salt-resistant" and "salt-sensitive." Human salt sensitivity is associated with structural and loading conditions that increase the risk for HF-PSF, including HTN, ventricular hypertrophy and diastolic dysfunction, arterial stiffening, and increased plasma volume. High dietary sodium intake induces oxidative stress in salt-sensitive humans. In humans with HTN and normal ventricular systolic function that do not have heart failure, increased oxidative stress predicts impaired exercise capacity, ventricular hypertrophy, diastolic dysfunction, arterial stiffening, and vascular endothelial dysfunction. The investigators have proposed that "salt sensitivity" and the accompanying oxidative stress on the typical high-sodium Western diet may contribute to the initiation and progression of HF-PSF.

In patients with HF-PSF, the investigators will relate dietary changes to biochemical and cardiovascular functional measures. The investigators will study subjects on ad-lib diet and and following three weeks of rigorous dietary modification with the Dietary Approaches to Stop Hypertension (DASH)/sodium-restricted diet (SRD). This diet is richer in natural antioxidants and lower in sodium than the usual American diet. The DASH/SRD is recommended to lower blood pressure in patients with HTN, and is particularly effective in elderly, obese, and salt-sensitive hypertensives. Dietary sodium restriction is recommended for all HF patients including those with HF-PSF. The investigators hypothesize that the DASH/SRD will have favorable effects on oxidative stress, ventricular and vascular function, and blood pressure control in patients with hypertensive HF-PSF.

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Conditions studied

  • Diastolic Heart Failure
  • Hypertensive Heart Disease

Keywords

  • Diet
  • Sodium
  • Hypertension
  • Potassium
  • Antioxidants
  • congestive heart failure
  • Heart failure with normal ejection fraction
  • Heart failure with preserved systolic function
03

In context

Hypertension

6,687 studies on the registry are indexed under Hypertension; 964 are open to participants now.

This study's enrollment of 14 is below the median of 90 across 4,994 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

University of Michigan is the lead sponsor of 1,475 studies on the registry; 196 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 128 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Satisfy European Society of Cardiology guidelines for the diagnosis of HF-PSF (Paulus WJ et al. Eur. Heart J. 2007;28:2539-2550).
  • Framingham criteria for heart failure satisfied
  • left ventricular ejection fraction ≥ 50% (contrast ventriculography, echocardiography, nuclear scintigraphy)
  • Diastolic dysfunction on previous echocardiogram/catheterization or evidence of abnormal neurohormonal activation (B-type natriuretic peptide (BNP) ≥ 100 pg/ml) with supporting evidence (atrial fibrillation, left atrial enlargement, left ventricular hypertrophy)
  • History of systemic hypertension
  • Willing to adhere to provided diet

Exclusion criteria

Exclusion Criteria:

  • New York Heart Association Class IV heart failure symptoms
  • Hospitalization for decompensated heart failure within past one month
  • Uncontrolled hypertension (seated systolic blood pressure ≥ 180 or diastolic blood pressure ≥ 110) at rest, on current antihypertensive regimen
  • Changes in medical regimen for heart disease or hypertension within past 1 month, including diuretic dose adjustment
  • Primary exercise limitation due to severe pulmonary disease
  • Poor echocardiographic windows
  • Worse than moderate mitral or aortic stenosis or insufficiency.
  • Serum potassium level > 5.0 mmol/L at baseline or prior history of serum potassium level > 6.0
  • Serum calcium/phosphorus product > 50 at baseline
  • Severe renal insufficiency (current estimated glomerular filtration rate \< 30 ml/min)
  • Severe anemia (hemoglobin \< 9 g/dL)
  • Uncontrolled diabetes mellitus (hemoglobin A1c > 9%)
  • Non-hypertensive cause of HF-PSF, e.g. amyloidosis, sarcoidosis, constrictive pericardial syndromes
  • Myocardial infarction or unstable angina, including new or worsening anginal syndrome, within the past three months
  • Uncontrolled arrhythmia (including non rate-controlled atrial fibrillation)
  • Terminal illness expected to result in death within six months or active solid-organ cancer
  • Psychiatric disorder or dementia with potential to compromise dietary adherence
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    Dietary intervention

    Diet patterned after the intervention in the DASH-Sodium trial (Sacks FM et al. New Engl J Med 2001;344(1):3-10). The diet includes higher quantities of fresh fruits and vegetables, whole grain products, and low-fat dairy products than the standard American diet. The target sodium content is 50 mmol per 2100 kcal, and the caloric content is intended to maintain body weight. The diet is designed, prepared, and packaged by research dietitians and all food and beverages are provided for study participants.

    Behavioral: DASH/sodium-restricted diet (SRD)

Interventions

  • BehavioralDASH/sodium-restricted diet (SRD)

    Baseline diet will be assessed via Block Food Frequency Questionnaire, and 24-hour urinary sodium, potassium, and 8-isoprostanes will be measured. Subjects will then be assigned to 21 days of the DASH/SRD, with all food and beverages provided. Adherence will be assessed through a three-day food diary at the midpoint of the intervention, and at the end of the study urinary sodium, potassium, and 8-isoprostanes will again be measured.

    Also known as: DASH diet, sodium-restricted diet, low sodium diet, DASH-sodium

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What researchers measure

Primary outcomes

  1. Brachial Artery Flow-mediated Dilation (FMD)

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Secondary outcomes

  1. Mean 24-hour Systolic Blood Pressure

    Change in 24-hour systolic blood pressure

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  2. Diurnal Variation in Ambulatory Blood Pressure

    Number of participants with non-dipping of nocturnal blood pressure - nighttime-to-daytime systolic BP ratio of \>= 0.9

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  3. Aortic Augmentation Index

    Aortic augmentation index is the ratio of the augmentation pressure to the central pulse pressure, expressed as a percentage. Both parameters are obtained via mathematical transformation of the radial pulse wave. The augmentation pressure represents the contribution of reflected waves to the pulse pressure. The central pulse pressure is the ratio between maximum aortic systolic pressure and minimum aortic diastolic pressure. A higher aortic augmentation index and central pulse pressure reflect increased arterial stiffness. Increased arterial stiffness is associated with an increased long-term risk of cardiovascular disease.

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  4. Carotid-femoral Pulse Wave Velocity

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  5. Ventricular Diastolic Function

    Lateral mitral annulus E/e' ratio

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  6. Six Minute Walk Test Distance

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  7. Urinary 8-isoprostanes

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Other outcomes

  1. EndoPAT Arterial Endothelial Function

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

  2. Estimated Glomerular Filtration Rate, Serum Potassium, Serum Calcium-phosphorus Product

    Safety measures to determine adverse effects of the provided DASH diet home-delivered meals

    Time frame: Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

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Results

Posted Oct 22, 2018

Participant flow

22 patients screened, 14 enrolled

Participant flow — Overall Study
MilestoneDietary Intervention
Started14
Completed13
Not completed1
Withdrew: Physician decision1

Outcome measures

PrimaryBrachial Artery Flow-mediated Dilation (FMD)
Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · % dilation
Brachial Artery Flow-mediated Dilation (FMD)
% dilationPre-dietary InterventionPost-dietary Intervention
Brachial Artery Flow-mediated Dilation (FMD)5 ± 58 ± 6
Statistical analysis
  • Pre-dietary Intervention vs Post-dietary Intervention · Wilcoxon matched-pairs · p = .17
SecondaryMean 24-hour Systolic Blood Pressure

Change in 24-hour systolic blood pressure

Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · mm Hg
Mean 24-hour Systolic Blood Pressure
mm HgPre-dietary InterventionPost-dietary Intervention
Mean 24-hour Systolic Blood Pressure130 ± 4123 ± 4
Statistical analysis
  • Pre-dietary Intervention vs Post-dietary Intervention · Wilcoxon matched-pairs tests · p = .02
SecondaryDiurnal Variation in Ambulatory Blood Pressure

Number of participants with non-dipping of nocturnal blood pressure - nighttime-to-daytime systolic BP ratio of \>= 0.9

Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Count of participants · Participants
Diurnal Variation in Ambulatory Blood Pressure
ParticipantsPre-Dietary InterventionPost-dietary Intervention
Diurnal Variation in Ambulatory Blood Pressure107
SecondaryAortic Augmentation Index

Aortic augmentation index is the ratio of the augmentation pressure to the central pulse pressure, expressed as a percentage. Both parameters are obtained via mathematical transformation of the radial pulse wave. The augmentation pressure represents the contribution of reflected waves to the pulse pressure. The central pulse pressure is the ratio between maximum aortic systolic pressure and minimum aortic diastolic pressure. A higher aortic augmentation index and central pulse pressure reflect increased arterial stiffness. Increased arterial stiffness is associated with an increased long-term risk of cardiovascular disease.

Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · percentage
Aortic Augmentation Index
percentagePre-Dietary InterventionPost-dietary Intervention
Aortic Augmentation Index29 ± 928 ± 10
SecondaryCarotid-femoral Pulse Wave Velocity
Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · m/s
Carotid-femoral Pulse Wave Velocity
m/sPre-Dietary InterventionPost-Dietary Intervention
Carotid-femoral Pulse Wave Velocity12.4 ± 311.0 ± 2.2
SecondaryVentricular Diastolic Function

Lateral mitral annulus E/e' ratio

Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · ratio
Ventricular Diastolic Function
ratioPre-Dietary InterventionPost-Dietary Intervention
Ventricular Diastolic Function12 ± 211 ± 2
SecondarySix Minute Walk Test Distance
Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · meters
Six Minute Walk Test Distance
metersPre-Dietary InterventionPost-Dietary Intervention
Six Minute Walk Test Distance313 ± 86337 ± 91
Statistical analysis
  • Pre-Dietary Intervention vs Post-Dietary Intervention · t-test, 2 sided · p = .006
SecondaryUrinary 8-isoprostanes
Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation
Reported as:
Mean · mmol F2-iso/mmol Cr
Urinary 8-isoprostanes
mmol F2-iso/mmol CrPre-Dietary InterventionPost-Dietary Intervention
Urinary 8-isoprostanes70 ± 2848 ± 15
Statistical analysis
  • Pre-Dietary Intervention vs Post-Dietary Intervention · t-test, 2 sided · p = .02
Other pre-specifiedEndoPAT Arterial Endothelial Function
Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Results for this outcome have not been posted.

Other pre-specifiedEstimated Glomerular Filtration Rate, Serum Potassium, Serum Calcium-phosphorus Product

Safety measures to determine adverse effects of the provided DASH diet home-delivered meals

Time frame:
Prior to and following 21 days of dietary intervention, i.e. day 1 and day 22 of participation

Results for this outcome have not been posted.

Adverse events

Collected over 25 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dietary Intervention—0/14 (0%)1/14 (7.1%)
Most frequent other events
Most frequent other events
EventDietary Intervention
hyperkalemiaMetabolism and nutrition disorders1/14

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Dietary Intervention
<=18 years0
Between 18 and 65 years0
>=65 years14
Age, Continuous
Age, Continuous(years)Dietary Intervention
Mean72 ± 10
Sex: Female, Male
Sex: Female, Male(Participants)Dietary Intervention
Female13
Male1
Region of Enrollment
Region of Enrollment(participants)Dietary Intervention
United States14
Body mass index
Body mass index(kg/m^2)Dietary Intervention
Mean35.5 ± 7.9
Hypertension
Hypertension(Participants)Dietary Intervention
Count of participants14
Participants with Chronic Kidney Disease
Participants with Chronic Kidney Disease(Participants)Dietary Intervention
Count of participants14
Coronary Artery Disease
Coronary Artery Disease(Participants)Dietary Intervention
Count of participants5

6 further baseline measures are reported on the registry.

08

Study locations

1 site
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
09

References and documents

Publications

  • Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256. PubMed 16855265 ↗
  • Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003 Jan 8;289(2):194-202. doi: 10.1001/jama.289.2.194. PubMed 12517230 ↗
  • Klotz S, Hay I, Zhang G, Maurer M, Wang J, Burkhoff D. Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction. Hypertension. 2006 May;47(5):901-11. doi: 10.1161/01.HYP.0000215579.81408.8e. Epub 2006 Apr 3. PubMed 16585423 ↗
  • Laffer CL, Bolterman RJ, Romero JC, Elijovich F. Effect of salt on isoprostanes in salt-sensitive essential hypertension. Hypertension. 2006 Mar;47(3):434-40. doi: 10.1161/01.HYP.0000202480.06735.82. Epub 2006 Jan 23. PubMed 16432053 ↗
  • Dekleva M, Celic V, Kostic N, Pencic B, Ivanovic AM, Caparevic Z. Left ventricular diastolic dysfunction is related to oxidative stress and exercise capacity in hypertensive patients with preserved systolic function. Cardiology. 2007;108(1):62-70. doi: 10.1159/000095883. Epub 2006 Sep 25. PubMed 17003543 ↗
  • Yugar-Toledo JC, Bonalume Tacito LH, Ferreira-Melo SE, Sousa W, Consolin-Colombo F, Irigoyen MC, Franchini K, Coelho OR, Moreno H Jr. Low-renin (volume dependent) mild-hypertensive patients have impaired flow-mediated and glyceryl-trinitrate stimulated vascular reactivity. Circ J. 2005 Nov;69(11):1380-5. doi: 10.1253/circj.69.1380. PubMed 16247215 ↗
  • Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101. PubMed 11136953 ↗
  • Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11. PubMed 17428822 ↗
  • Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S, Weder AB, Kovacs SJ, Kolias TJ. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013 Nov;6(6):1165-71. doi: 10.1161/CIRCHEARTFAILURE.113.000481. Epub 2013 Aug 28. PubMed 23985432 ↗
  • Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, Wells JM, Weder AB. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction. Hypertension. 2012 Nov;60(5):1200-6. doi: 10.1161/HYPERTENSIONAHA.112.202705. Epub 2012 Oct 1. PubMed 23033371 ↗
  • Mathew AV, Seymour EM, Byun J, Pennathur S, Hummel SL. Altered Metabolic Profile With Sodium-Restricted Dietary Approaches to Stop Hypertension Diet in Hypertensive Heart Failure With Preserved Ejection Fraction. J Card Fail. 2015 Dec;21(12):963-7. doi: 10.1016/j.cardfail.2015.10.003. Epub 2015 Oct 20. PubMed 26497755 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 15, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00939640
Lead sponsor
University of Michigan
Responsible party
Scott L. Hummel (Assistant Professor, University of Michigan) — Principal investigator
First posted
Jul 15, 2009
Start date
Jul 2009
Primary completion
May 2011
Completion
May 2011
Results posted
Oct 22, 2018
Last update
Oct 15, 2019

Study contacts

Scott L Hummel, MD MS
principal investigator · University of Michigan

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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