A Phase 2 interventional study of N-Acetylcysteine (NAC) and Placebo in Angina Attacks and Non Obstructive Coronary Artery Disease, sponsored by University of Adelaide. Not yet recruiting at 1 site in Australia. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-24.
Sponsored by University of Adelaide · Phase 2, Interventional, and Treatment
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.
Background:
Angina with Non-Obstructive Coronary Arteries (ANOCA) refers to a condition where patients experience chronic angina despite having no significant coronary artery blockages. This condition affects 50-70% of women undergoing elective angiography, in stark contrast to just 7-17% of men. Many experience a prolonged delay in diagnosis, resulting in notable decreases in functional capacity.
NAC has been shown to reduce oxidative stress and potentiate the vasodilatory and antiaggregatory effects of nitrates, potentially reducing microvascular damage and improving myocardial perfusion, hence presenting a promising therapeutic option for ANOCA patients. Although there are no established clinical guidelines for ANOCA management, standard therapy typically includes both long-acting and short-acting nitrates to alleviate anginal symptoms. However, many ANOCA patients continue to experience symptoms despite standard therapy. As such, this trial will assess the beneficial effects of NAC therapy in ANOCA women.
Primary Objectives: To determine the effect of NAC 600mg twice daily on angina frequency in patients with ANOCA who experience angina at least 3 times/week as assessed by an angina diary.
Secondary Objective: The secondary objectives of this study are:
i. To assess the impact of NAC therapy (600mg twice daily) on quality of life/health status, utilising generic (EQ-5D) and disease-specific (SAQ-7) health status instruments to evaluate the following PROMs:
a) Short-acting nitrate consumption (i.e., Glyceryl trinitrate (GTN) spray use) b) Duration of angina episodes c) Severity of angina episodes
Safety objectives i. Emergency Department (ED) presentations with Chest pain ii. Hospital admissions with chest pain iii. Major Adverse Coronary Events (MACE) Clinic Assessments: Visit 1: Screening: Screening assessments will be completed within 14 days prior to administration of NAC/Placebo.
Criteria for Evaluation: Angina diary: Results will be considered significant if participants have significantly (p\<0.05) reduced features of angina extracted from angina diary during the NAC phase compared to placebo phase.
SAQ-7: Results will be considered significant if participants demonstrate reduced physical limitations \& angina frequency and improved quality of life during NAC phase compared to placebo phase.
EQ-5D: Results will be considered significant if participants demonstrate improved quality of life scores during NAC Phase compared to placebo phase.
Statistical Methods: Efficacy Endpoint NAC's anti-anginal efficacy will be undertaken by blinded analysis of the angina diary endpoints and other endpoints. The comparison between patients with respect to treatment order will be analysed utilising a linear mixed-effects model.
Safety Endpoint Frequency and severity of adverse events.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's planned enrollment of 25 is below the median of 124 across 3,006 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →University of Adelaide is the lead sponsor of 42 studies on the registry; 6 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
i. anaemia ( \<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 ( and/or AST 2 x (ULN) or ALP 2 x ULN or 1.5 x ULN) f) Severe renal impairment ( \<30mL/min) or on dialysis. g) Pregnancy or lactation. h) Untreated hypertension i) Unwilling, or unable, to give , 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)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
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
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
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.
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.
Time frame: 8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)
Frequency of Short-acting nitrate consumption (i.e., Glyceryl trinitrate (GTN) spray use)
Short-acting nitrate consumption (i.e., Glyceryl trinitrate (GTN) spray use), self reported on angina diary
Time frame: 8 weeks (4 weeks treatment compared to 4 weeks placebo)
Frequency of prolonged angina episodes (ie episodes persisting > 20 minutes)
Frequency of prolonged angina episodes (ie episodes persisting \> 20 minutes) assessed from patient's self reported angina diary
Time frame: 8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)
Angina frequency score as assessed by Seattle Angina Questionnaire (SAQ)
The Seattle Angina Questionnaire (SAQ) is a tool used to assess the health-related quality of life in patients with angina, especially those with coronary artery disease (CAD). Patients report the frequency of their angina episodes, including both exertional and spontaneous chest pain, based on structured response options. The score is then converted to a 0-100 scale, with higher scores indicating less frequent angina and better symptom control.
Time frame: 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
The Angina-Related Physical Limitations Score is a subscale of the Seattle Angina Questionnaire (SAQ) that evaluates the extent to which angina symptoms restrict a patient's ability to perform daily physical activities. Patients rate the difficulty they experience in performing activities such as walking, climbing stairs, or carrying groceries due to their angina. Responses are scored on a 0-100 scale, where higher scores indicate fewer physical limitations and better functional status.
Time frame: 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
Patients assess the impact of angina on their overall quality of life, including emotional well-being, physical limitations, and social functioning. The score is converted to a 0-100 scale, with higher scores reflecting better quality of life and less impact from angina.
Time frame: End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)
Patient satisfaction with angina therapy score as assessed on Seattle Angina Questionnaire
Patients rate their satisfaction with the current treatment regimen for managing angina, based on structured questions related to the effectiveness, convenience, and side effects of therapy. The score is converted to a 0-100 scale, with higher scores indicating greater satisfaction.
Time frame: End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)
Overall physical health as assessed by EQ-5D Questionnaire
EQ-5D is a standardized questionnaire developed by the EuroQol Group to measure health-related quality of life. Patients assess their overall physical health through the EQ-5D, which includes questions related to mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The score is then converted to a 0-100 scale, with higher scores indicating better overall physical health and less impact from the condition.
Time frame: End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks)
Severity score of angina episodes as assessed on angina diary
Angina severity score (scored as 1-10), 10 being most intense assessed from patient's self-reported angina diary
Time frame: 8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)
Plan to share: No — The collected data contains confidential patient health information. De-identified data may be made available upon request, but it will not be publicly accessible due to the inclusion of confidential patient health information. Access will be granted in accordance with ethical guidelines and institutional policies, ensuring that all requests are reviewed and approved before data is shared
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Studies of the drug tested here: Acetylcysteine
University of Adelaide