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

Breast Cancer Clinical Trial

— NARNIA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05732051
• Other study ID #: 2021/156064(REK)
• Status: Recruiting
• Phase: Phase 2
• Start date: March 16, 2023
• Est. completion date: September 30, 2035

Study information

• Verified date: February 2023
• Source: University Hospital, Akershus
• Contact: Torbjørn Omland, MD, PhD
• Phone: +47 40107050
• Email: torbjorn.omland[@]medisin.uio.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2035
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cardiotoxicity
• Heart Failure
• Metastatic Breast Cancer

Intervention

Dietary Supplement:
• Nicotinamide Riboside
Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy
• Placebo
Matching placebo b.i.d as long as the patient is receiving anthracycline therapy

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog	Akershus

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Akershus	ChromaDex, Inc., Helse Sor-Ost, Norwegian Breast Cancer Association, Norwegian Cancer Society

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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