Exercise Therapy for Women With ANOCA (ANOCA Exercise)

July 24, 2026 updated by: NHS Greater Glasgow and Clyde

Exercise Therapy for Women With ANOCA: a Randomised, Controlled Trial

Angina is a feeling of chest pain or discomfort which can happen if there is reduced blood flow to the heart. Patients can experience angina with no obstructive coronary arteries (ANOCA) which is a difficult condition to treat (ie relieve angina) since few randomised, controlled therapy trials have been undertaken for ANOCA. Until now, angina has been mainly studied in men even though women are at least two-fold more likely than men to experience ANOCA.

In 2023, a Scientific Statement from the American Heart Association affirmed that resistance exercise training can improve or maintain muscle mass and strength and confer favourable physiological and clinical effects on cardiovascular disease and risk factors. Resistance exercise has not been assessed in ANOCA and it offers an important opportunity to study non drug alternatives to treatment for women.

This study will use a resistance based exercise programme to investigate if symptoms of ANOCA can be improved in women. It will recruit at least 76 patients (maximum 152 patients) across 13 hospitals in the UK and the Netherlands.

The study will use a randomised wait list control design. This means all participants will be offered the intervention, but the randomisation will decide when they undergo it.

It is part of a platform of trials for women with ANOCA. We are also setting up a drug study called ANOCA Therapy and a cohort study called ANOCA- Diagnosis.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

There is a gap in knowledge on evidence-based therapy for ANOCA. Stratified medicine is a population-level diagnostic approach for identifying endotypes in a heterogenous population of all-comers. An endotype is defined as a subtype of a condition, which must be characterised by a distinct functional or pathophysiological mechanism.

Use of quantitative noninvasive and invasive diagnostic methods, such as magnetic resonance imaging and coronary function tests involving acetylcholine testing, enables more accurate identification and discrimination of causal endotypes of ANOCA. This is especially relevant for women with ANOCA who have historically been under-recognised.

Quantitative diagnostic methods should bring an end to empirical therapy, therapeutic nihilism and sex disparities in ANOCA.

Precision medicine is different. Precision medicine targets the individual (and their endotype) with a mechanism informed therapy. Accordingly, in this Wellcome Leap Visible project, we will employ a stratified medicine diagnostic approach in women with suspected ANOCA undergoing invasive CFTs in multiple hospitals and then employ a precision medicine strategy by offering each woman an endotype-informed therapy option.

Resistance exercise has not been previously investigated in ANOCA and it therefore represents a novel therapeutic option. This lifestyle intervention will increase the range of trial options, maximize patient choice for participation, and facilitate timely delivery of this project. The beneficial effects of resistance exercise on cardiovascular function have recently been endorsed in a Scientific Statement from the American Heart Association and further supported by a systematic review and favourable experience in our recent randomized trial in Long COVID.

In 2023, a Scientific Statement from the American Heart Association affirmed that resistance exercise training can improve or maintain muscle mass and strength and confer favourable physiological and clinical effects on cardiovascular disease and risk factors. In 19 men with coronary artery disease and endothelial dysfunction, indicated by abnormal acetylcholine-induced coronary vasoconstriction, a randomized controlled trial of aerobic exercise training demonstrated improvements in endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels. The intervention involved an exercise program six times per day for at least 10 minutes. These results were promising but came with major limitations: no women were included in the study and the exercise program is both burdensome and impractical.

Resistance exercise has not been assessed in ANOCA. Inclusion of a non-CTIMP (lifestyle intervention) brings strategic advantages to our ANOCA platform. A non-medicinal intervention provides an accessible therapy option for women of child-bearing age and for those who may prefer not to participate in an investigational drug trial. This non-CTIMP may also become an option for women who withdraw from a CTIMP, or who complete a CTIMP and are willing to continue into a second trial. The basket trial of resistance exercise may include participants who have completed a precision medicine CTIMP who then wish to participate in the resistance exercise trial or vice versa.

Study Type

Interventional

Enrollment (Estimated)

76

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Basildon, United Kingdom
        • Basildon University Hospital
      • Bath, United Kingdom
        • Royal United Hospital Bath
      • Cambridge, United Kingdom
        • Royal Papworth Hospital
      • Glasgow, United Kingdom, G51 4TF
        • Queen Elizabeth University Hospital Clinical Research Facility
        • Contact:
      • Leeds, United Kingdom
        • Leeds General Infirmary
      • London, United Kingdom
        • Kings College Hospital
      • London, United Kingdom
        • Brompton Hospital
      • London, United Kingdom
        • Guy and St Thomas Hospital
      • Newcastle upon Tyne, United Kingdom
        • Freeman Hospital
        • Contact:
          • Vijay Kunadian
      • Nottingham, United Kingdom
        • Nottingham City Hospital
      • Sunderland, United Kingdom
        • Sunderland Royal Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Angina with no obstructive coronary arties (ANOCA)
  2. Myocardial perfusion reserve or coronary flow reserve recorded within three years
  3. Seattle Angina Questionnaire frequency score ≤60
  4. Duke Activity Status Index ≤34
  5. Female sex

Exclusion Criteria:

  1. Age <18 years
  2. Unable to provide informed consent
  3. - Unable to comply with the protocol
  4. Pregnancy
  5. Currently undertaking resistance exercise activities

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Allocated to exercise intervention first
Behavioral: Resistance based exercise
Participants will undergo daily resistance based exercise for 8 weeks
Active Comparator: Control
Allocated to exercise intervention second
Behavioral: Resistance based exercise
Participants will undergo daily resistance based exercise for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seattle Angina Questionnaire
Time Frame: Change from Baseline to Week 9
The Seattle Angina Questionnaire a validated 19-item patient-reported survey used to measure coronary artery disease and angina treatment efficacy. Patients will complete on paper or electronically. The scores range from 0 to 100, with higher scores indicating less frequent angina, improved function, and better quality of life.
Change from Baseline to Week 9

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial perfusion reserve (MPR)
Time Frame: Change from baseline to week 9
The ratio of maximum blood flow in the heart muscle under stress compared to resting flow
Change from baseline to week 9
Handgrip strength using hand dynamometer
Time Frame: Change from baseline to week 9
Measured in Kgs. This is used as a proxy for overall body strength with lower measures indicating less strength.
Change from baseline to week 9
Short Physical Performance Battery (SPPB)
Time Frame: Change from baseline to week 9
Used as a proxy for fitness
Change from baseline to week 9
Brief Illness perception Questionnaire (Brief IPQ)
Time Frame: Change from baseline to week 9
A nine-item scale designed to rapidly assess the cognitive and emotional representations of illness. It consists of 9 items: 8 are scored on a 0-10 scale, and item 9 is an open-ended question assessing perceived causes. The total score (0-80) is calculated by summing the first 8 items, with items 3, 4, and 7 reverse scored. Higher scores generally reflect a more threatening perception of the illness
Change from baseline to week 9
Patient Health Questionnaire-4 of (PHQ4)
Time Frame: Change from Baseline to Week 9
An ultra-brief screening tool used to assess core symptoms of anxiety and depression. Higher scores indicate greater feelings of anxiety and depression.
Change from Baseline to Week 9
Duke Activity Status Index (DASI)
Time Frame: From Baseline to Week 9
A 12-item, self-administered questionnaire used to estimate a patient's functional capacity and peak oxygen uptake. Scores range from 0 to 58.2, with higher scores indicating better physical fitness and lower risk
From Baseline to Week 9
EQ-5D (EQ-5D-5L)
Time Frame: Change from Baseline to Week 9

The EQ-5D evaluates health across 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). It yields three metrics: a 5-digit health profile string, a weighted index value, and a 0-100 self-rated Visual Analogue Scale (VAS) score.

For the 5-digit health profile string higher individual numbers indicate worse health problems.

For the weighted index value a score of 1 indicates perfect health, while 0 represents death.

For the visual analogue score higher numbers here indicate better health
Change from Baseline to Week 9
International Physical Activity Questionnaire (IPAQ)
Time Frame: Change from Baseline to Week 9
Used to obtain comparable estimates of physical activity between populations and countries. Higher scores indicate greater physical activity.
Change from Baseline to Week 9
Fatigue severity scale questionnaire
Time Frame: Change from Baseline to Week 9
Rates level of fatigue. 9 statements assess how fatigue impacts daily life. Each statement is rated on a 7-point Likert scale, ranging from 1 (strongly disagree) to 7 (strongly agree). Higher scores indicate greater fatigue.
Change from Baseline to Week 9
Short Form Post-Exercise Malaise Questionnaire
Time Frame: Change from Baseline to Week 9
measures symptom exacerbation by assessing frequency and severity of symptoms. Higher scores reflect a stronger indication of post exercise malaise.
Change from Baseline to Week 9
Episodes of care (primary, secondary, physiotherapy, rehabilitation)
Time Frame: Week 9
How many times participants engaged with services
Week 9
Hospitalisation for any reason by electronic health record review (where available) up to 4 months (Visit 3)
Time Frame: Week 17
Review of medical notes to see if the patient has been in hospital
Week 17

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

The University of Glasgow

Investigators

  • Principal Investigator: Colin Berry, The University of Glasgow

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 14, 2026

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

July 20, 2026

First Submitted That Met QC Criteria

July 24, 2026

First Posted (Actual)

July 29, 2026

Study Record Updates

Last Update Posted (Actual)

July 29, 2026

Last Update Submitted That Met QC Criteria

July 24, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN26CA170

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A decision will be made by the TSC once the study has ended.

IPD Sharing Time Frame

After the study has completed

IPD Sharing Access Criteria

Bone fide collaboration request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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