Clinical trial NCT05732051: Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients
Official title: Effect of Nicotinamide Riboside on Myocardial and Skeletal Muscle Injury and Function in Patients With Metastatic Breast Cancer Receiving Anthracyclines
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Breast Cancer
Cancer Therapy-Related Cardiac Dysfunction
Cardiotoxicity
Heart Failure
Keywords: Breast Cancer
Anthracyclines
Niagen
Nicotinamide riboside
Nicotinamide adenine dinucleotide
Reactive oxygen species
Cardiac Dysfunction
Cardio-oncology
Cardiotoxicity
Cancer Therapy-Related Cardiac Dysfunction
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: ChromaDex, Inc.
name: Norwegian Cancer Society
name: Norwegian Breast Cancer Association
name: Helse Sor-Ost
First posted: 2023-02-16
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomised, placebo-controlled
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Whether the administration of nicotinamide riboside can prevent the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR), compared to placebo.
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Secondary outcomes:
measure: Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin T (hs-cTnT)
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin I (hs-cTnI)
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Other outcomes:
measure: Pharmacological endpoint: Change in circulating Nicotinamide adenine dinucleotide (NAD+) concentration from baseline to end of blinded therapy.
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less reduction in left ventricular diastolic function measured by echocardiography
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less aortic stiffness measured by CMR
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less skeletal muscle injury
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less skeletal muscle injury
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less worsening in health-related quality of life
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less worsening in health-related quality of life
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
measure: Tertiary objective: Less worsening in health-related quality of life
timeFrame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Locations:
city: Lørenskog
country: Norway
facility: Akershus University Hospital
state: Akershus
Study officials:
affiliation: University Hospital, Akershus
name: Torbjørn Omland, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: