NARNIA: Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients
Study Details
Study Description
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, we want to answer whether nicotinamide riboside can prevent cancer-related cardiac dysfunction in metastatic breast cancer patients scheduled for anthracycline therapy. 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, and various measurements of change in left ventricular systolic function determined by CMR and echocardiography. Additional assessments are functional capacity (handgrip strength test, 6-minute walk test), quality of life (EORTC QLQ-C30, EQ-5D-5L and Chalder Fatigue Scale) and circulating creatine kinase and myoglobin.
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Treatment Arm The 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. |
Dietary Supplement: Nicotinamide Riboside
Niagen 500mg b.i.d as long as the patient is receiving anthracycline therapy
Other Names:
|
| Placebo Comparator: Placebo Control Arm The 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. |
Dietary Supplement: Placebo
Matching placebo b.i.d as long as the patient is receiving anthracycline therapy
|
Outcome Measures
Primary Outcome Measures
- Whether the administration of nicotinamide riboside (Niagen®) 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
- Assess whether the administration of Niagen® 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 Niagen® 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 LV GLS, as determined by echocardiography
- Assess whether the administration of Niagen® 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 LV GCS and GLS, as determined by CMR
- Assess whether the administration of Niagen® 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 LV end-systolic volume measured by CMR
- To assess whether the administration of Niagen® is associated with less myocardial injury measured by cardiac troponin T [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 cardiac hs-cTnT
- To assess whether the administration of Niagen® is associated with less myocardial injury measured by cardiac troponin I [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 cardiac hs-cTnI
- To assess whether the administration of Niagen® 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
- To assess whether the administration of Niagen® 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 force generated by handgrip strength test
Other Outcome Measures
- Pharmacological endpoint: Change in circulating 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 LC-MS analyses.
- 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 T2 measured by CMR
- 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 T1 measured by CMR
- 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 T1rho 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 LV 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 NT-proBNP
- 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 cardiac myosin binding protein C (cMyC)
- 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)
- 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 myoglobin
- 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 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 European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
- 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 European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L). Each dimension in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Women with metastatic breast cancer (stage IV breast cancer) scheduled for anthracycline-containing chemotherapy (weekly doxorubicin, EC-60 etc.)
-
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 Niagen® tablet
-
Contraindications or inability to undergo CMR examination
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Akershus University Hospital | Lørenskog | Akershus | Norway | 1478 |
Sponsors and Collaborators
- University Hospital, Akershus
- ChromaDex, Inc.
- Norwegian Cancer Society
- Norwegian Breast Cancer Association
- Helse Sor-Ost
Investigators
- Principal Investigator: Torbjørn Omland, MD, PhD, University Hospital, Akershus
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021/156064(REK)