Trial Outcomes & Findings for Hypertrophic Regression With N-Acetylcysteine in HCM (NCT NCT01537926)

NCT ID: NCT01537926

Last Updated: 2021-11-02

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: at the time of enrollment
• Results posted on: 2021-11-02

Participant Flow

Participant milestones

Measure	N-acetylcysteine (NAC) N-acetylcysteine (NAC) 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to minic NAC 600mg capsule
Overall Study STARTED	29	13
Overall Study COMPLETED	24	11
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hypertrophic Regression With N-Acetylcysteine in HCM

Baseline characteristics by cohort

Measure	N-acetylcysteine (NAC) n=29 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to minic NAC 600mg capsule	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	12 Participants n=7 Participants	34 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	50.7 years STANDARD_DEVIATION 15.0 • n=5 Participants	47.6 years STANDARD_DEVIATION 15.1 • n=7 Participants	49.15 years STANDARD_DEVIATION 0.56 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	10 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	12 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	29 Participants n=5 Participants	13 Participants n=7 Participants	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: at the time of enrollment

Outcome measures

Measure	N-acetylcysteine (NAC) n=29 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Recruitment as Assessed by Number of Participants Who Enrolled to the Study	29 Participants	13 Participants

PRIMARY outcome

Timeframe: from baseline to 12 months

Outcome measures

Measure	N-acetylcysteine (NAC) n=29 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Retention as Assessed by Number of Participants Who Completed the Study	24 Participants	11 Participants

PRIMARY outcome

Timeframe: from baseline to 12 months

Population: Data are reported for participants for whom all pill bottles were returned to the study team. It was not known whether the returned bottles contained placebo or NAC; therefore, the data for both arms are reported together.

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.

Outcome measures

Measure	N-acetylcysteine (NAC) n=30 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Compliance as Assessed by Percentage of Pills Taken by Participant	92 percentage of pills taken Standard Deviation 0.0878	—

PRIMARY outcome

Timeframe: from baseline to 12 months

Outcome measures

Measure	N-acetylcysteine (NAC) n=29 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Number of Participants With Side Effects Attributable to the Intervention	0 Participants	0 Participants

PRIMARY outcome

Timeframe: baseline

Population: Data are reported for all participants who completed the study.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography	18.88 millimeters (mm) Standard Deviation 4.59	18.00 millimeters (mm) Standard Deviation 3.97

PRIMARY outcome

Timeframe: 12 months

Population: Data are reported for all participants who completed the study.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Interventricular Septal Thickness (IVST) as Assessed by Echocardiography	17.92 millimeters (mm) Standard Deviation 3.3	17.82 millimeters (mm) Standard Deviation 4.87

SECONDARY outcome

Timeframe: 12 months

Population: Data are reported for all participants who completed the study.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography	21.88 millimeters (mm) Standard Deviation 5.29	21.55 millimeters (mm) Standard Deviation 3.8

SECONDARY outcome

Timeframe: baseline

Population: Data are reported for all participants who completed the study.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Left Ventricular End-systolic Diameter (LVESD) as Assessed by Echocardiography	22.13 millimeters (mm) Standard Deviation 6.06	22.64 millimeters (mm) Standard Deviation 5.16

SECONDARY outcome

Timeframe: baseline

Population: Data are reported for all participants who completed the study.

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.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Left Ventricular Mass (LVM) as Assessed by Echocardiography	269.65 g/m^2 Standard Deviation 94.17	292.80 g/m^2 Standard Deviation 107.50

SECONDARY outcome

Timeframe: 12 months

Population: Data are reported for all participants who completed the study.

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.

Outcome measures

Measure	N-acetylcysteine (NAC) n=24 Participants N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=11 Participants Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Left Ventricular Mass (LVM) as Assessed by Echocardiography	281.98 g/m^2 Standard Deviation 81.75	290.44 g/m^2 Standard Deviation 99.81

Adverse Events

N-acetylcysteine (NAC)

Serious events: 5 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	N-acetylcysteine (NAC) n=29 participants at risk N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 participants at risk Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. 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. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Respiratory, thoracic and mediastinal disorders Pneumonia	6.9% 2/29 • Number of events 2 • 12 months	0.00% 0/13 • 12 months
Vascular disorders Cerebrovascular accident	6.9% 2/29 • Number of events 2 • 12 months	0.00% 0/13 • 12 months
Nervous system disorders Seizure	3.4% 1/29 • Number of events 1 • 12 months	0.00% 0/13 • 12 months
General disorders Chest pain	3.4% 1/29 • Number of events 1 • 12 months	0.00% 0/13 • 12 months

Other adverse events

Measure	N-acetylcysteine (NAC) n=29 participants at risk N-acetylcysteine 600mg by mouth every 12 hours for 90 days. N-acetylcysteine 1200mg by mouth every 12 hours for 270 days 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.	Placebo n=13 participants at risk Placebo 1 cap by mouth every 12 hours for 90 days. Placebo 2 caps by mouth every 12 hours for 270 days. 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. Placebo: sugar pill manufactured to mimic NAC 600mg capsule
Skin and subcutaneous tissue disorders Skin Rash	6.9% 2/29 • Number of events 2 • 12 months	0.00% 0/13 • 12 months

Additional Information

Dr. Ali J. Marian

UTHealth Science Center at Houston

Phone: 713-500-2310

Email: Ali.J.marian@uth.tmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place