Breast Cancer, Cancer Therapy-Related Cardiac Dysfunction, Cardiotoxicity, Heart Failure, Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, Anthracyclines, Niagen, Nicotinamide riboside, Nicotinamide adenine dinucleotide, Reactive oxygen species, Cardiac Dysfunction, Cardio-oncology, Cardiotoxicity, Cancer Therapy-Related Cardiac Dysfunction
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.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside
Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy
DIETARY_SUPPLEMENTPlacebo
Matching placebo b.i.d as long as the patient is receiving anthracycline therapy
Sponsors
ChromaDex, Inc.
Norwegian Cancer Society
Norwegian Breast Cancer Association
Helse Sor-Ost
University Hospital, Akershus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.
Intervention model description
Double-blind, randomised, placebo-controlled
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography | 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 LVEF, as determined by echocardiography |
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR | 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 left ventricular global circumferential strain (GCS) and GLS, as determined by CMR |
| 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 |
| 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 capacity | 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 distance in meters during 6-minute walk test |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacological endpoint: Change in circulating Nicotinamide adenine dinucleotide (NAD+) concentration from baseline to end of blinded therapy. | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses) |
| Tertiary objective: Less worsening in health-related quality of life | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Quality of life measured by Chalder Fatigue Scale. Items are rated on a 4-point Likert scale (0 = better than usual, 1 = no more than usual, 2 = worse than usual, 3 = much worse than usual), with higher scores indicating greater fatigue. |
| Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Change in transverse relaxation time (T2) measured by CMR |
| Tertiary objective: Less reduction in left ventricular diastolic function measured by echocardiography | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Change in left ventricular diastolic function as measured by echocardiography |
| Tertiary objective: Less aortic stiffness measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Change in the aortic pulse wave velocity measured by CMR |
| Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP) |
| Tertiary objective: Less skeletal muscle injury | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy | Change in circulating creatine kinase (CK) |
Countries
Norway
Contacts
Primary ContactTorbjørn Omland, MD, PhD
Backup ContactVictoria Vinje, MD
Outcome results
None listed