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Hypertrophic CardiomyopathyPhase 1HALTNCT01537926

Hypertrophic Regression With N-Acetylcysteine in HCM

A Phase 1 study testing N-acetylcysteine in people with Hypertrophic Cardiomyopathy, run by The University of Texas Health Science Center, Houston at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypertrophic Cardiomyopathy
What is being tested?
N-acetylcysteine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
1 siteUnited States
Study dates
Jan 2012to 31 Dec 2016
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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:
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Pilot Feasibility Study With N-acetylcystein (NAC) in Patients With HCM Caused by Sarcomere Proteins Mutations

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.

Being tested
N-acetylcysteine, Placebo
Keywords
HALT, HCM
Medical subject headings
Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • N-acetylcysteineDrug

    Also called NAC

    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.

  • PlaceboDrug

    Also called Sugar pill

    sugar pill manufactured to minic NAC 600mg capsule

Study groups in NCT01537926
Study groupRoleWhat they receive
N-acetylcysteine (NAC)ExperimentalN-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days
Receives: Drug: N-acetylcysteine
PlaceboPlacebo comparatorPlacebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: at the time of enrollment

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

    Measured: 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.

    Measured: from baseline to 12 months

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

    Measured: from baseline to 12 months

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

    Measured: baseline

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

    Measured: 12 months

Secondary outcomes (4)

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

    Measured: 12 months

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

    Measured: 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.

    Measured: 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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2012 (estimated)
  2. Study startJan 2012
  3. Primary completion31 Dec 2016
  4. Study completion31 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01537926
Sponsor's protocol ID
HALT-HCM
Other IDs
IR34HL105563
Acronym
HALT
Status last verified
Nov 2021
First submitted
15 Feb 2012
Last updated
2 Nov 2021
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing N-acetylcysteine in people with Hypertrophic Cardiomyopathy, run by The University of Texas Health Science Center, Houston at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recruitment as Assessed by Number of Participants Who Enrolled to the Study (time frame: at the time of enrollment). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01537926, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.

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