Hypertrophic Regression With N-Acetylcysteine in HCM

NCT01537926 | Completed Phase 1 Results DMC

• 2 other identifiers: HALT-HCMIR34HL105563
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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 it has any beneficial effects.

Conditions

Hypertrophic Cardiomyopathy

Keywords

HALT; HCM

Outcome Measures

Primary Outcomes (6)

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

  at the time of enrollment

• Retention as Assessed by Number of Participants Who Completed the Study

  from baseline to 12 months

• 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.

  from baseline to 12 months

• Number of Participants With Side Effects Attributable to the Intervention

  from baseline to 12 months

• Interventricular Septal Thickness (IVST) as Assessed by Echocardiography

  baseline

• Interventricular Septal Thickness (IVST) as Assessed by Echocardiography

  12 months

Secondary Outcomes (4)

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

  12 months

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

  baseline

• Left Ventricular Mass (LVM) as Assessed by Echocardiography

  baseline

• Left Ventricular Mass (LVM) as Assessed by Echocardiography

  12 months

Study Arms (2)

N-acetylcysteine (NAC)

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

N-acetylcysteine DRUG

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

N-acetylcysteine (NAC)

Placebo DRUG

sugar pill manufactured to minic NAC 600mg capsule

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 29540445 RESULT

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Acetylcysteine; Sugars

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Carbohydrates

Limitations and Caveats

The small sample size of the study prohibits from making firm conclusions about efficacy of NAC in hypertrophic cardiomyopathy (HCM).

Results Point of Contact

• Title: Dr. Ali J. Marian
• Organization: UTHealth Science Center at Houston

Ali.J.marian@uth.tmc.edu

713-500-2310

Study Officials

• Ali J. Marian, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor , Cardiovascular Genetics, IMM

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: February 23, 2012
• Study Start: January 1, 2012
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: November 2, 2021
• Results First Posted: November 2, 2021

Record last verified: 2021-11

Locations

US (1)