The Anti-Anginal Effects of N-Acetylcysteine (NAC) in Patients with Angina and Non-Obstructive Coronary Arteries (ANOCA)

NCT06890507 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025/HRE00080
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine if N-acetylcysteine (NAC) can reduce angina frequency in women with Angina with Non-Obstructive Coronary Arteries (ANOCA). It will also assess the impact of NAC on health status and quality of life. The main questions it aims to answer are: (i) Does NAC reduce the number of angina episodes per week? (ii) How does NAC affect quality of life and symptom burden in ANOCA patients? (iii) Does NAC reduce the need for short-acting nitrate use? Researchers will compare NAC to a placebo in a randomized, double-blind, placebo-controlled crossover study to determine its effectiveness. Participants will receive treatment with NAC 600mg twice daily for 4 weeks (28 days) and matched placebo for 4 weeks (28 days) in a computer-generated random order giving a total dosing period of 8 weeks. There will be a 2-week washout between the two treatment periods. The effectiveness of N-Acetylcysteine (NAC) will be assessed using the following measures: Angina Diary: Participants will record the frequency and severity of their angina episodes. Seattle Angina Questionnaire-7 (SAQ-7): Participants will complete this questionnaire to assess physical limitations, angina frequency, and quality of life. EuroQol 5-Dimension (EQ-5D) Questionnaire: Participants will rate their overall health and quality of life.

Conditions

Angina Attacks; Non Obstructive Coronary Artery Disease

Keywords

ANOCA; Angina with Non Obstructive Coronary Arteries; N-acetylcysteine

Outcome Measures

Primary Outcomes (1)

• Frequency of angina episodes recorded in angina diary.

  Number of angina episodes recorded in angina diary. The angina diary is developed to record the frequency, duration, severity, and reliever of chest pain episodes. Participant record their angina episodes throughout the study period.

  8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)

Secondary Outcomes (8)

• Frequency of Short-acting nitrate consumption (i.e., Glyceryl trinitrate (GTN) spray use)

  8 weeks (4 weeks treatment compared to 4 weeks placebo)

• Frequency of prolonged angina episodes (ie episodes persisting > 20 minutes)

  8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)

• Angina frequency score as assessed by Seattle Angina Questionnaire (SAQ)

  End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)

• Angina-related physical limitations score as assessed on Seattle Angina Questionnaire

  End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)

• Angina-related quality of life score as assessed on Seattle Angina Questionnaire

  End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)

Study Arms (2)

Oral NAC 600mg (twice daily) Intervention Arm

EXPERIMENTAL

This arm will assess the effects of oral N-Acetylcysteine (NAC) at a dose of 600mg twice daily in patients with ANOCA. Participants will receive the NAC treatment for a 4-week period.

Drug: N-Acetylcysteine (NAC)

Placebo 600mg twice daily

PLACEBO COMPARATOR

This arm will serve as the placebo comparator in the crossover study design. Participants will receive a placebo treatment that is identical in appearance to the NAC medication but contains no active ingredient.The order of treatment (NAC vs placebo) is randomized and participants remain blinded throughout the study.

Drug: Placebo

Interventions

N-Acetylcysteine (NAC) DRUG

The investigational product for this study is NAC 600 mg capsules. The NAC drug substance is sourced from a Good Manufacturing Practice (GMP)-certified supplier by Syntro Health Pty Ltd and tested on receipt

Oral NAC 600mg (twice daily) Intervention Arm

Placebo DRUG

To ensure appropriate blinding and to match the physical characteristics of the NAC capsules, the placebo capsules will be filled with dicalcium phosphate (DCP). DCP has been selected over microcrystalline cellulose due to the weight requirements of the NAC formulation.

Placebo 600mg twice daily

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female sex
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Female patients aged ≥18 years
• No obstructive CAD (defined as either absence of epicardial lesions with ≥50% luminal narrowing in any coronary artery segment on coronary angiography or normal findings on computed tomography (CT) angiogram, indicating the absence of significant stenosis) to account for chest pain symptoms.
• Chest pain occurring ≥3 times/week in the preceding two weeks.

You may not qualify if:

• Known allergy to NAC or its components.
• Acute myocardial infarction admission within the preceding month (hospital admission for prolonged angina paint associated with a cardiac troponin level above the 99th percentile, with a subsequent rise or fall).
• Secondary causes of angina including:
• i. clinically significant anaemia (haemoglobin \<100g/dL) ii. uncontrolled atrial fibrillation (ventricular response rate \>108bpm) iii. haemodynamically significant aortic stenosis (mean valve gradient ≥40mmHg) d) Known concomitant disease with life expectance of less than 1 year. e) Abnormalities in liver function tests suggesting hepatic impairment (ALT and/or AST 2 x upper limit of normal (ULN) or ALP 2 x ULN or Bilirubin 1.5 x ULN) f) Severe renal impairment (eGFR \<30mL/min) or on dialysis. g) Pregnancy or lactation. h) Untreated hypertension i) Unwilling, or unable, to give informed consent, including due to severe psychiatric conditions affecting informed consent process or compliance.
• j) History of substance abuse. k) Currently taking Chloroquine. l) Serious or unstable medical conditions that may interfere with the study, as determined by the PI.
• m) Concomitant participation in another clinical trial or research study (except where in the opinion of the PI, the participant could benefit from enrolling in another trial)

Sponsors & Collaborators

• University of Adelaide: lead

Study Sites (1)

The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

Location

MeSH Terms

Interventions

Acetylcysteine

Intervention Hierarchy (Ancestors)

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

Study Officials

• John Beltrame, PhD

  University of Adelaide

  PRINCIPAL INVESTIGATOR

• Sivabaskari Pasupathy, PhD

  University of Adelaide

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sivabaskari Pasupathy, PhD

CONTACT

+6182228685; sivabaskari.pasupathy@adelaide.edu.au

John Beltrame, PhD

CONTACT

+6182226740; john.beltrame@adelaide.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Statistician
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Post doctoral Research Fellow

Model Details: Randomised, double-blind, placebo-controlled crossover study assessing the anti-anginal effect and impact on health status of NAC 600mg twice daily in patients with ANOCA experiencing angina at least 3 times/week32

Study Record Dates

• First Submitted: March 16, 2025
• First Posted: March 24, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)