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NCT Number: NCT05732051

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Cancer Therapy-related Cardiac Dysfunction Cardiotoxicity Cardiovascular Diseases Chemically-Induced Disorders Drug-Related Side Effects and Adverse Reactions Heart Diseases Heart Failure Metastatic Breast Cancer Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Radiation Injuries Skin Diseases Skin and Connective Tissue Diseases Wounds and Injuries

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Akershus University Hospital

Lørenskog, Akershus, 1478, Norway

Location status: Recruiting

Location contact

Evandro F Fang, PhD

SUB_INVESTIGATOR

Jürgen Geisler, MD, PhD

SUB_INVESTIGATOR

Torbjørn Omland, MD, PhD

CONTACT

[email protected]

+47 40107050

Torbjørn Omland, MD, PhD

PRINCIPAL_INVESTIGATOR

Victoria Vinje, MD

CONTACT

[email protected]

+47 92033665

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nicotinamide riboside

Dietary Supplement

Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy

Other names: Niagen (serial number 85932490, registration number 4606519)

Placebo

Dietary Supplement

Matching placebo b.i.d as long as the patient is receiving anthracycline therapy

Primary outcomes

  1. Whether the administration of nicotinamide riboside can prevent the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR), compared to placebo.

    Time frame: 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 outcomes

  1. Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography

    Time frame: 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

  2. Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography

    Time frame: 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 longitudinal strain (GLS), as determined by echocardiography

  3. Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR

    Time frame: 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

  4. Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR

    Time frame: 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 end-systolic volume measured by CMR

  5. To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin T (hs-cTnT)

    Time frame: 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

  6. To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin I (hs-cTnI)

    Time frame: 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

  7. To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity

    Time frame: 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

  8. To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity

    Time frame: 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 outcomes

  1. Pharmacological endpoint: Change in circulating Nicotinamide adenine dinucleotide (NAD+) concentration from baseline to end of blinded therapy.

    Time frame: 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)

  2. Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR

    Time frame: 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

  3. Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR

    Time frame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

    Change in longitudinal relaxation time (T1) measured by CMR

  4. Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR

    Time frame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

    Change in T1 rho measured by CMR

  5. Tertiary objective: Less reduction in left ventricular diastolic function measured by echocardiography

    Time frame: 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

  6. Tertiary objective: Less aortic stiffness measured by CMR

    Time frame: 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

  7. Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin

    Time frame: 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)

  8. Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin

    Time frame: 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)

  9. Tertiary objective: Less skeletal muscle injury

    Time frame: 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)

  10. Tertiary objective: Less skeletal muscle injury

    Time frame: Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

    Change in circulating myoglobin

  11. Tertiary objective: Less worsening in health-related quality of life

    Time frame: 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.

  12. Tertiary objective: Less worsening in health-related quality of life

    Time frame: 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 / Quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

  13. Tertiary objective: Less worsening in health-related quality of life

    Time frame: 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Torbjørn Omland, MD, PhD

CONTACT

[email protected]

+47 40107050

Victoria Vinje, MD

CONTACT

[email protected]

+47 92033665

Sponsors and collaborators

Lead sponsor

University Hospital, Akershus

Other

Collaborators

  • ChromaDex, Inc.
  • Helse Sor-Ost
  • Norwegian Breast Cancer Association
  • Norwegian Cancer Society

Registry information

Official study title

Effect of Nicotinamide Riboside on Myocardial and Skeletal Muscle Injury and Function in Patients With Metastatic Breast Cancer Receiving Anthracyclines

Acronym: NARNIA

Important dates

Study start
2023
Primary completion
2025
Study completion
2035
First posted
Feb 16, 2023
Registry last updated
Mar 17, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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