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CompletedNCT01537926HALTUpdated Nov 2, 2021Results posted

Hypertrophic Regression With N-Acetylcysteine in HCM

A Phase 1 interventional study of N-acetylcysteine and Placebo in Hypertrophic Cardiomyopathy, sponsored by The University of Texas Health Science Center, Houston. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-02.

Sponsored by The University of Texas Health Science Center, Houston · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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 it has any beneficial effects.

Read the 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). Data will be gathered on the recruitment, accrual, retention, and compliance rates of HCM patients randomized to treatment with a placebo or two escalating doses of NAC. Likewise, any potential side effects will be determined and the effect size of NAC on indices of cardiac hypertrophy will be estimated. HCM, the main focus of the study team's 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. The study team has 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. The study team proposes to test their 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. The study aims to 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 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.

02

Conditions studied

  • Hypertrophic Cardiomyopathy

Keywords

  • HALT
  • HCM
03

In context

Cardiomyopathies

1,176 studies on the registry are indexed under Cardiomyopathies; 287 are open to participants now.

This study's enrollment of 42 is below the median of 51 across 609 interventional studies indexed under Cardiomyopathies.

Browse Cardiomyopathies studies →

Lead sponsor

The University of Texas Health Science Center, Houston is the lead sponsor of 880 studies on the registry; 209 are open to participants now.

Of its 170 completed or terminated interventional studies of FDA-regulated products, 140 (82%) have results posted.

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

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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)
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
42 participants (actual)

Study arms

  • 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

  • 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: Placebo

Interventions

  • DrugN-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.

    Also known as: NAC

  • DrugPlacebo

    sugar pill manufactured to minic NAC 600mg capsule

    Also known as: Sugar pill

06

What researchers measure

Primary outcomes

  1. Recruitment as Assessed by Number of Participants Who Enrolled to the Study

    Time frame: at the time of enrollment

  2. Retention as Assessed by Number of Participants Who Completed the Study

    Time frame: from baseline to 12 months

  3. Compliance as Assessed by Percentage of Pills Taken by Participant

    Participants returned all pill bottles to the study team, and the number of pills not taken by the participant (that is, the number of pills remaining in the bottles) were counted. Compliance is reported as percentage of pills taken by the participant.

    Time frame: from baseline to 12 months

  4. Number of Participants With Side Effects Attributable to the Intervention

    Time frame: from baseline to 12 months

  5. Interventricular Septal Thickness (IVST) as Assessed by Echocardiography

    Time frame: baseline

  6. Interventricular Septal Thickness (IVST) as Assessed by Echocardiography

    Time frame: 12 months

Secondary outcomes

  1. Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography

    Time frame: 12 months

  2. Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography

    Time frame: baseline

  3. Left Ventricular Mass (LVM) as Assessed by Echocardiography

    Left Ventricular Mass (LVM) is the weight of the left heart and is estimated from the echocardiographic measurements that include left ventricular wall thickness and the chamber diameter. The weight is calculated in grams and then normalized to body surface area (m\^2), with LVM reported as g/m\^2.

    Time frame: baseline

  4. Left Ventricular Mass (LVM) as Assessed by Echocardiography

    Left Ventricular Mass (LVM) is the weight of the left heart and is estimated from the echocardiographic measurements that include left ventricular wall thickness and the chamber diameter. The weight is calculated in grams and then normalized to body surface area (m\^2), with LVM reported as g/m\^2.

    Time frame: 12 months

07

Results

Posted Nov 2, 2021
Limitations and caveats
The small sample size of the study prohibits from making firm conclusions about efficacy of NAC in hypertrophic cardiomyopathy (HCM).

Participant flow

Participant flow — Overall Study
MilestoneN-acetylcysteine (NAC)Placebo
Started2913
Completed2411
Not completed52

Outcome measures

PrimaryRecruitment as Assessed by Number of Participants Who Enrolled to the Study
Time frame:
at the time of enrollment
Reported as:
Count of participants · Participants
Recruitment as Assessed by Number of Participants Who Enrolled to the Study
ParticipantsN-acetylcysteine (NAC)Placebo
Recruitment as Assessed by Number of Participants Who Enrolled to the Study2913
PrimaryRetention as Assessed by Number of Participants Who Completed the Study
Time frame:
from baseline to 12 months
Reported as:
Count of participants · Participants
Retention as Assessed by Number of Participants Who Completed the Study
ParticipantsN-acetylcysteine (NAC)Placebo
Retention as Assessed by Number of Participants Who Completed the Study2411
PrimaryCompliance as Assessed by Percentage of Pills Taken by Participant

Participants returned all pill bottles to the study team, and the number of pills not taken by the participant (that is, the number of pills remaining in the bottles) were counted. Compliance is reported as percentage of pills taken by the participant.

Time frame:
from baseline to 12 months
Reported as:
Mean · percentage of pills taken
Compliance as Assessed by Percentage of Pills Taken by Participant
percentage of pills takenAll Participants
Compliance as Assessed by Percentage of Pills Taken by Participant92 ± 0.0878
PrimaryNumber of Participants With Side Effects Attributable to the Intervention
Time frame:
from baseline to 12 months
Reported as:
Count of participants · Participants
Number of Participants With Side Effects Attributable to the Intervention
ParticipantsN-acetylcysteine (NAC)Placebo
Number of Participants With Side Effects Attributable to the Intervention00
PrimaryInterventricular Septal Thickness (IVST) as Assessed by Echocardiography
Time frame:
baseline
Reported as:
Mean · millimeters (mm)
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography
millimeters (mm)N-acetylcysteine (NAC)Placebo
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography18.88 ± 4.5918.00 ± 3.97
PrimaryInterventricular Septal Thickness (IVST) as Assessed by Echocardiography
Time frame:
12 months
Reported as:
Mean · millimeters (mm)
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography
millimeters (mm)N-acetylcysteine (NAC)Placebo
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography17.92 ± 3.317.82 ± 4.87
SecondaryLeft Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography
Time frame:
12 months
Reported as:
Mean · millimeters (mm)
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography
millimeters (mm)N-acetylcysteine (NAC)Placebo
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography21.88 ± 5.2921.55 ± 3.8
SecondaryLeft Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography
Time frame:
baseline
Reported as:
Mean · millimeters (mm)
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography
millimeters (mm)N-acetylcysteine (NAC)Placebo
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography22.13 ± 6.0622.64 ± 5.16
SecondaryLeft Ventricular Mass (LVM) as Assessed by Echocardiography

Left Ventricular Mass (LVM) is the weight of the left heart and is estimated from the echocardiographic measurements that include left ventricular wall thickness and the chamber diameter. The weight is calculated in grams and then normalized to body surface area (m\^2), with LVM reported as g/m\^2.

Time frame:
baseline
Reported as:
Mean · g/m^2
Left Ventricular Mass (LVM) as Assessed by Echocardiography
g/m^2N-acetylcysteine (NAC)Placebo
Left Ventricular Mass (LVM) as Assessed by Echocardiography269.65 ± 94.17292.80 ± 107.50
SecondaryLeft Ventricular Mass (LVM) as Assessed by Echocardiography

Left Ventricular Mass (LVM) is the weight of the left heart and is estimated from the echocardiographic measurements that include left ventricular wall thickness and the chamber diameter. The weight is calculated in grams and then normalized to body surface area (m\^2), with LVM reported as g/m\^2.

Time frame:
12 months
Reported as:
Mean · g/m^2
Left Ventricular Mass (LVM) as Assessed by Echocardiography
g/m^2N-acetylcysteine (NAC)Placebo
Left Ventricular Mass (LVM) as Assessed by Echocardiography281.98 ± 81.75290.44 ± 99.81

Adverse events

Collected over 12 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
N-acetylcysteine (NAC)0/29 (0%)5/29 (17.2%)2/29 (6.9%)
Placebo0/13 (0%)0/13 (0%)0/13 (0%)
Most frequent serious events
Most frequent serious events
EventN-acetylcysteine (NAC)Placebo
PneumoniaRespiratory, thoracic and mediastinal disorders2/290/13
Cerebrovascular accidentVascular disorders2/290/13
SeizureNervous system disorders1/290/13
Chest painGeneral disorders1/290/13
Most frequent other events
Most frequent other events
EventN-acetylcysteine (NAC)Placebo
Skin RashSkin and subcutaneous tissue disorders2/290/13

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)N-acetylcysteine (NAC)PlaceboTotal
<=18 years000
Between 18 and 65 years221234
>=65 years718
Age, Continuous
Age, Continuous(years)N-acetylcysteine (NAC)PlaceboTotal
Mean50.7 ± 15.047.6 ± 15.149.15 ± 0.56
Sex: Female, Male
Sex: Female, Male(Participants)N-acetylcysteine (NAC)PlaceboTotal
Female7310
Male221032
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)N-acetylcysteine (NAC)PlaceboTotal
Hispanic or Latino415
Not Hispanic or Latino251237
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)N-acetylcysteine (NAC)PlaceboTotal
United States291342
08

Study locations

1 site
  • The University of Texas Health Science Center at Houston
    Houston, Texas 77030, United States
09

References and documents

Publications

  • Marian AJ, Tan Y, Li L, Chang J, Syrris P, Hessabi M, Rahbar MH, Willerson JT, Cheong BY, Liu CY, Kleiman NS, Bluemke DA, Nagueh SF. Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy (HALT-HCM): A Randomized, Placebo-Controlled, Double-Blind Pilot Study. Circ Res. 2018 Apr 13;122(8):1109-1118. doi: 10.1161/CIRCRESAHA.117.312647. Epub 2018 Mar 14. PubMed 29540445 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 2, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01537926
Lead sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institutes of Health (NIH)
Responsible party
Ali. J. Marian (Professor , Cardiovascular Genetics, IMM, The University of Texas Health Science Center, Houston) — Principal investigator
First posted
Feb 23, 2012
Start date
Jan 2012
Primary completion
Dec 31, 2016
Completion
Dec 31, 2016
Results posted
Nov 2, 2021
Last update
Nov 2, 2021

Study contacts

Ali J. Marian, MD
principal investigator · The University of Texas Health Science Center, Houston

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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