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Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients

Phase 2
Recruiting
Conditions
Cancer Therapy-Related Cardiac Dysfunction
Cardiotoxicity
Heart Failure
Breast Cancer
Metastatic Breast Cancer
Interventions
Dietary Supplement: Placebo
Dietary Supplement: Nicotinamide Riboside
Registration Number
NCT05732051
Lead Sponsor
University Hospital, Akershus
Brief Summary

Breast cancer is the most common form of cancer in women. Modern breast cancer treatments have led to increased survival, but at the same time, increased risk for cardiotoxicity and development of heart failure. In this study, the investigators want to evaluate whether nicotinamide riboside can prevent cancer-related cardiac dysfunction in metastatic breast cancer patients scheduled for anthracycline therapy. Further, the investigators will evaluate change in signs of skeletal muscle injury and functional capacity.

Detailed Description

The trial is prospective, randomised, double-blind and placebo-controlled. The primary objective is change in left ventricular ejection fraction (LVEF), determined by cardiac MRI (CMR). Secondary objectives are change in circulating high-sensitivity cardiac troponin I and T (hs-TnI and hs-TnT), Creatine Kinase (CK) and myoglobin, and various measurements of change in left ventricular systolic function determined by CMR and echocardiography. Additional assessments are evaluation of the patient's functional capacity and the patients will be asked to fill out questionnaires to assess quality of life.

60 patients will be randomised in a 1:1 ratio. The duration of blinded therapy will depend on the duration of anthracycline therapy. All patients will be examined at baseline and 3 months, and if the patient is scheduled for extended anthracycline therapy, an additional examination will be performed at 6 months.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
60
Inclusion Criteria
  • Women with metastatic breast cancer (stage IV breast cancer) scheduled for anthracycline-containing chemotherapy
  • Eastern Cooperative Oncology Group performance status 0-2

Exclusion Criteria

  • Age <18 years
  • Acute myocardial infarction within the last three months
  • Participation in another pharmaceutical clinical trial of an investigational medicinal product (IMP) less than 4 weeks prior to inclusion or use of other investigational drugs within 5 half-lives of enrollment, whichever is longer
  • Conditions that would affect the participants to comply with the study protocol as psychiatric or mental disorders, alcohol abuse or other substance abuse, suspected poor drug compliance, language barriers
  • Life expectancy < 6 months
  • Known allergy to any of the components in the Nicotinamide Riboside (Niagen®) tablet
  • Contraindications or inability to undergo CMR examination
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo Control ArmPlaceboThe patients randomised into this arm of the trial will receive a matching placebo b.i.d. The duration of treatment is equivalent to the description in the treatment arm.
Treatment ArmNicotinamide RibosideThe patients randomised into this arm of the trial will receive 500 mg Nicotinamide Riboside b.i.d. The duration of blinded therapy will depend on the duration of anthracycline therapy, and will for some patients last for 3 months, others for 6 months.
Primary Outcome Measures
NameTimeMethod
Whether the administration of nicotinamide riboside can prevent the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR), compared to placebo.Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization to end of blinded therapy.

Secondary Outcome Measures
NameTimeMethod
Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiographyBaseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

From randomization to the end of blinded therapy:

Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography

To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin T (hs-cTnT)Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

From randomization to the end of blinded therapy:

Change in circulating hs-cTnT

Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMRBaseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

From randomization to the end of blinded therapy:

Change in left ventricular end-systolic volume measured by CMR

To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin I (hs-cTnI)Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

From randomization to the end of blinded therapy:

Change in circulating hs-cTnI

To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacityBaseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

From randomization to the end of blinded therapy:

Change in force generated by handgrip strength test

Trial Locations

Locations (1)

Akershus University Hospital

🇳🇴

Lørenskog, Akershus, Norway

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