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

NCT05732051 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2021/156064(REK)
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

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.

  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

Secondary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

Other Outcomes (13)

• 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

• 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

• 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

Study Arms (2)

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.

Dietary Supplement: Nicotinamide Riboside

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.

Dietary Supplement: Placebo

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

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

Also known as: Niagen (serial number 85932490, registration number 4606519)

Treatment Arm

Placebo DIETARY_SUPPLEMENT

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

Placebo Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with metastatic breast cancer (stage IV breast cancer) scheduled for anthracycline-containing chemotherapy
• Eastern Cooperative Oncology Group performance status 0-2

You may not qualify if:

• Age \<18 years
• Acute myocardial infarction within the last three months
• 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

Sponsors & Collaborators

• University Hospital, Akershus: lead
• ChromaDex, Inc.: collaborator
• Norwegian Cancer Society: collaborator
• Norwegian Breast Cancer Association: collaborator
• Helse Sor-Ost: collaborator

Study Sites (1)

Akershus University Hospital

Lørenskog, Akershus, 1478, Norway

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity; Heart Failure

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• Torbjørn Omland, MD, PhD

  University Hospital, Akershus

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Torbjørn Omland, MD, PhD

CONTACT

+47 40107050; torbjorn.omland@medisin.uio.no

Victoria Vinje, MD

CONTACT

+47 92033665; victoria.vinje@ahus.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Double-blind, randomised, placebo-controlled

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 16, 2023
• Study Start: March 16, 2023
• Primary Completion: August 1, 2025
• Study Completion (Estimated): September 30, 2035
• Last Updated: March 17, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)