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| Name | Class |
|---|---|
| ChromaDex, Inc. | INDUSTRY |
| Norwegian Cancer Society | OTHER |
| Norwegian Breast Cancer Association | UNKNOWN |
| Helse Sor-Ost |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm | Active Comparator | 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. |
|
| Placebo Control Arm | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotinamide Riboside | Dietary Supplement | Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Whether the administration of nicotinamide riboside can prevent the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR), compared to placebo. | Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography | From randomization to the end of blinded therapy: Change in LVEF, as determined by echocardiography | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacological endpoint: Change in circulating Nicotinamide adenine dinucleotide (NAD+) concentration from baseline to end of blinded therapy. | Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses) | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
Inclusion Criteria:
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Torbjørn Omland, MD, PhD | Contact | +47 40107050 | torbjorn.omland@medisin.uio.no | |
| Victoria Vinje, MD | Contact | +47 92033665 | victoria.vinje@ahus.no |
| Name | Affiliation | Role |
|---|---|---|
| Torbjørn Omland, MD, PhD | University Hospital, Akershus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Akershus University Hospital | Recruiting | Lørenskog | Akershus | 1478 | Norway |
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| OTHER_GOV |
Double-blind, randomised, placebo-controlled
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The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.
| Placebo | Dietary Supplement | Matching placebo b.i.d as long as the patient is receiving anthracycline therapy |
|
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography | From randomization to the end of blinded therapy: Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR | From randomization to the end of blinded therapy: Change in left ventricular global circumferential strain (GCS) and GLS, as determined by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR | From randomization to the end of blinded therapy: Change in left ventricular end-systolic volume measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin T (hs-cTnT) | From randomization to the end of blinded therapy: Change in circulating hs-cTnT | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin I (hs-cTnI) | From randomization to the end of blinded therapy: Change in circulating hs-cTnI | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity | From randomization to the end of blinded therapy: Change in distance in meters during 6-minute walk test | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity | From randomization to the end of blinded therapy: Change in force generated by handgrip strength test | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR | Change in transverse relaxation time (T2) measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR | Change in longitudinal relaxation time (T1) measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR | Change in T1 rho measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less reduction in left ventricular diastolic function measured by echocardiography | Change in left ventricular diastolic function as measured by echocardiography | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less aortic stiffness measured by CMR | Change in the aortic pulse wave velocity measured by CMR | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin | Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP) | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin | Chance in circulating cardiac myosin binding protein C (cMyC) | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less skeletal muscle injury | Change in circulating creatine kinase (CK) | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less skeletal muscle injury | Change in circulating myoglobin | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less worsening in health-related quality of life | 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. | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less worsening in health-related quality of life | 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 / Quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| Tertiary objective: Less worsening in health-related quality of life | 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). | Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D066126 | Cardiotoxicity |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| C018613 | nicotinamide-beta-riboside |
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