We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Hypertrophic Regression With N-Acetylcysteine in HCM (HALT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01537926
Recruitment Status : Completed
First Posted : February 23, 2012
Last Update Posted : May 4, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of the sudy is to conduct a small study to gather the preliminary data for future lage scale clinical studies that will be designed test the potential beneficial effect of over-the counter study anti-oxidant drug called N-acetylcysteine (NAC) in patients with a heart muscle condition called Hypertrophic Cardiomyopathy (HCM). The present study is a pilot feasibility study, the investigators want to find out whether the investigators can recruit and retain patients with HCM in the study and whether these patients can tolerate this drug and can stay on one year. Likewise, the investigators want to find out any potential side effects that this drug might have and estimate whether ii has any beneficial effects.

Condition or disease Intervention/treatment Phase
Hypertrophic Cardiomyopathy Drug: N-acetylcysteine Drug: Placebo Phase 1

Detailed Description:

The primary objective is to perform a pilot study in patients with hypertrophic cardiomyopathy (HCM) and mutations in genes encoding sarcomere proteins to assess safety and gather the pre-requisite data for subsequent robust randomized placebo-controlled efficacy studies with N-acetylcysteine (NAC). We will gather data on the recruitment, accrual, retention, and compliance rates of HCM patients randomized to treatment with a placebo or two escalating doses of NAC. Likewise, we will determine any potential side effects and estimate the effect size of NAC on indices of cardiac hypertrophy.

HCM, the main focus of our research during the past two decades, is the most common cause of sudden cardiac death (SCD) in the young and an important cause of morbidity in the elderly. Despite its clinical impact, there is no effective pharmacological therapy for HCM. None of the current pharmacological therapies reverses or attenuates cardiac hypertrophy or reduces the risk of SCD in adults. Cardiac hypertrophy, the quintessential clinical feature of human HCM, is a major determinant of morbidity and the risk of SCD. Regression of cardiac hypertrophy is expected to improve morbidity and decrease the risk of SCD in HCM, as observed upon regression of load-dependent cardiac hypertrophy.

We have generated transgenic rabbit and mouse models of HCM and shown that cardiac hypertrophy and fibrosis could be reversed through genetic or pharmacological interventions. Results with NAC, a precursor to glutathione; the largest intracellular thiol pool against oxidative stress, were most promising. In three independent studies in two different transgenic models of HCM (rabbits and mouse), treatment with NAC completely reversed cardiac hypertrophy and fibrosis and improved indices of diastolic function. The ultimate goal of every physician-scientist is to apply the bench discoveries at the bedside. We propose to test our findings in the animal models in humans with HCM caused by sarcomere protein mutations. The use of NAC is also supported by data showing increased oxidative stress in human HCM. Moreover, NAC has been used extensively in humans and has a well-established safety profile. Resources including patients with sarcomere protein mutations are available to successfully complete a randomized placebo-controlled (N=25) pilot study to test two escalating doses of NAC (N=50), administered for one year. We will determine recruitment, accrual, retention and compliance rates; tolerability, safety and side effects; and estimate the effect size of NAC on the indices of cardiac hypertrophy, as determined by serial cardiac magnetic resonance imaging (MRI) at the baseline and after one year of treatment. Only HCM patients with sarcomere proteins mutations will be included to exclude phenocopy. The Core centers will interpret the phenotypic data to assure homogeneity. Data Coordinating Center will assist in the research design, planning and conduct of the study and analysis of the data. The findings will set the stage for large-scale robust randomized placebo-control efficacy studies.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Feasibility Study With N-acetylcystein (NAC) in Patients With HCM Caused by Sarcomere Proteins Mutations
Study Start Date : January 2012
Primary Completion Date : December 31, 2016
Study Completion Date : December 31, 2016

Arms and Interventions

Arm Intervention/treatment
Experimental: N-acetylcysteine (NAC)
N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days
Drug: N-acetylcysteine
NAC 600mg capsule or matching Placebo , 1 twice daily for 90 days, then increase to NAC 1,200mg or matching placebo, 2 capsules twice daily for 270 days.
Other Name: NAC
Drug: Placebo
sugar pill manufactured to minic NAC 600mg capsule
Other Name: Sugar pill
Placebo Comparator: Placebo
Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days.
Drug: N-acetylcysteine
NAC 600mg capsule or matching Placebo , 1 twice daily for 90 days, then increase to NAC 1,200mg or matching placebo, 2 capsules twice daily for 270 days.
Other Name: NAC
Drug: Placebo
sugar pill manufactured to minic NAC 600mg capsule
Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :
  1. Recruitment rate [ Time Frame: 36 months ]

    We will determine the estimates and 95% confidence intervals (CIs) of

    • The recruitment and accrual rates
    • Patient compliance rate with the two escalating doses of NAC and placebo
    • Patients developing side effects
    • Patients who complete the intended 12 months treatment with NAC and placebo.
    • Baseline estimates and effect size of NAC on indices of cardiac hypertrophy mainly LVM indexed to body surface area (LVMI).

Secondary Outcome Measures :
  1. indices of cardiac mass and function [ Time Frame: 36 months ]
    Changes in LV maximum and mean wall thicknesses; LVED volume (EDDV), LV end systolic volume (ESV), circumferential LV strain, LVEF, peak filling rate (PFR), peak ejection rate (PER) and time to PER; and macroscopic interstitial myocardial fibrosis, as defined by delayed MRI following gadolinium contrast administration.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with primary cardiac hypertrophy, non-dilated LV cavity and preserved LV systolic function, hence, the diagnosis of HCM, who have at least an LV end diastolic (LVSD) wall thickness of at least 15 mm on a 2D echocardiogram and
  • Known to have mutations in genes encoding sarcomeric proteins

Exclusion Criteria:

  • Hypersensitivity to NAC
  • Individuals younger than 18 years old (in the pilot study)
  • Phenocopy conditions, diagnosed clinically or genetically
  • Patients who have undergone transcatheter (alcohol) septal ablation within 6 months.
  • Individuals (typically family members) with causal mutations but an LVSD wall thickness of <15 mm
  • Patients with concomitant diseases such as:

    • Significant coronary artery disease >70% luminal diameter stenosis in ny of the major coronary arteries (if known);
    • Valvular heart diseases (more than mild aortic stenosis and mitral regurgitation, the latter judged to be due to primary mitral valve abnormalities);
    • Uncontrolled hypertension, defined as systolic blood pressure of

      • 140 mmHg and diastolic blood pressure of ≥90 mmHg on medication, mean of three measurements at rest);
    • Other significant medical problems, such as moderate to severe chronic renal failure (GFR<45 ml/min/1.73m2), advanced liver disease, cancer, or other disabling conditions
  • Pregnant women, nursing mothers and those who plan pregnancy during the study period
  • Those with active asthma (albeit the concern is relevant to nebulizer form but not oral formulations)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01537926

United States, Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
National Institutes of Health (NIH)
Principal Investigator: Ali J. Marian, MD The University of Texas Health Science Center, Houston
More Information

Responsible Party: Ali. J. Marian, Professor , Cardiovascular Genetics, IMM, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01537926     History of Changes
Other Study ID Numbers: HALT-HCM
First Posted: February 23, 2012    Key Record Dates
Last Update Posted: May 4, 2017
Last Verified: May 2017

Keywords provided by Ali. J. Marian, The University of Texas Health Science Center, Houston:

Additional relevant MeSH terms:
Cardiomyopathy, Hypertrophic
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs