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

Primary Purpose

Breast Cancer, Metastatic Breast Cancer, Cancer Therapy-Related Cardiac Dysfunction

Status
Recruiting
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Nicotinamide Riboside
Placebo
Sponsored by
University Hospital, Akershus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring Breast Cancer, Anthracyclines, Niagen, Nicotinamide riboside, Nicotinamide adenine dinucleotide, Reactive oxygen species, Cardiac Dysfunction, Cardio-oncology, Cardiotoxicity, Cancer Therapy-Related Cardiac Dysfunction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Akershus University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Treatment Arm

Placebo Control Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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
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
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
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
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

Full Information

First Posted
January 25, 2023
Last Updated
March 16, 2023
Sponsor
University Hospital, Akershus
Collaborators
ChromaDex, Inc., Norwegian Cancer Society, Norwegian Breast Cancer Association, Helse Sor-Ost
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1. Study Identification

Unique Protocol Identification Number
NCT05732051
Brief Title
Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients
Acronym
NARNIA
Official Title
Effect of Nicotinamide Riboside on Myocardial and Skeletal Muscle Injury and Function in Patients With Metastatic Breast Cancer Receiving Anthracyclines
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 16, 2023 (Actual)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
September 30, 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Akershus
Collaborators
ChromaDex, Inc., Norwegian Cancer Society, Norwegian Breast Cancer Association, Helse Sor-Ost

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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, 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, randomised, placebo-controlled
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo Control Arm
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nicotinamide Riboside
Other Intervention Name(s)
Niagen (serial number 85932490, registration number 4606519)
Intervention Description
Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Matching placebo b.i.d as long as the patient is receiving anthracycline therapy
Primary Outcome Measure Information:
Title
Whether the administration of nicotinamide riboside can prevent the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR), compared to placebo.
Description
Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization 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
Secondary Outcome Measure Information:
Title
Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography
Description
From randomization to the end of blinded therapy: Change in LVEF, as determined by echocardiography
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by echocardiography
Description
From randomization to the end of blinded therapy: Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR
Description
From randomization to the end of blinded therapy: Change in left ventricular global circumferential strain (GCS) and GLS, as determined by CMR
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Assess whether the administration of nicotinamide riboside is associated with less reduction in left ventricular systolic function measured by CMR
Description
From randomization to the end of blinded therapy: Change in left ventricular end-systolic volume 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
Title
To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin T (hs-cTnT)
Description
From randomization to the end of blinded therapy: Change in circulating hs-cTnT
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
To assess whether the administration of nicotinamide riboside is associated with less myocardial injury measured by high-sensitive cardiac troponin I (hs-cTnI)
Description
From randomization to the end of blinded therapy: Change in circulating hs-cTnI
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity
Description
From randomization to the end of blinded therapy: Change in distance in meters during 6-minute walk test
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
To assess whether the administration of nicotinamide riboside is associated with less worsening in functional capacity
Description
From randomization to the end of blinded therapy: Change in force generated by handgrip strength test
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Other Pre-specified Outcome Measures:
Title
Pharmacological endpoint: Change in circulating Nicotinamide adenine dinucleotide (NAD+) concentration from baseline to end of blinded therapy.
Description
Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses)
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
Description
Change in transverse relaxation time (T2) 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
Title
Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
Description
Change in longitudinal relaxation time (T1) 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
Title
Tertiary objective: Less myocardial injury expressed as oedema or fibrosis by CMR
Description
Change in T1 rho 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
Title
Tertiary objective: Less reduction in left ventricular diastolic function measured by echocardiography
Description
Change in left ventricular diastolic function as 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
Title
Tertiary objective: Less aortic stiffness measured by CMR
Description
Change in the aortic pulse wave velocity 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
Title
Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin
Description
Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP)
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less myocardial injury and dysfunction measured by cardiac biomarkers other than troponin
Description
Chance in circulating cardiac myosin binding protein C (cMyC)
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less skeletal muscle injury
Description
Change in circulating creatine kinase (CK)
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less skeletal muscle injury
Description
Change in circulating myoglobin
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less worsening in health-related quality of life
Description
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.
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less worsening in health-related quality of life
Description
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.
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy
Title
Tertiary objective: Less worsening in health-related quality of life
Description
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).
Time Frame
Baseline, 3 months, 6 months for patients receiving extended chemotherapy, and extended follow up 12 months after initiation of chemotherapy

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Torbjørn Omland, MD, PhD
Phone
+47 40107050
Email
torbjorn.omland@medisin.uio.no
First Name & Middle Initial & Last Name or Official Title & Degree
Victoria Vinje, MD
Phone
+47 92033665
Email
victoria.vinje@ahus.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Torbjørn Omland, MD, PhD
Organizational Affiliation
University Hospital, Akershus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Akershus University Hospital
City
Lørenskog
State/Province
Akershus
ZIP/Postal Code
1478
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torbjørn Omland, MD, PhD
Phone
+47 40107050
Email
torbjorn.omland@medisin.uio.no
First Name & Middle Initial & Last Name & Degree
Victoria Vinje, MD
Phone
+47 92033665
Email
victoria.vinje@ahus.no
First Name & Middle Initial & Last Name & Degree
Torbjørn Omland, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jürgen Geisler, MD, PhD
First Name & Middle Initial & Last Name & Degree
Evandro F Fang, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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