Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Heart Failure

Cardiotoxicity

Breast Diseases

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Heart Diseases

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Niacinamide

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Vitamin B Complex

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Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

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.

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

Nicotinamide Riboside

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

Placebo

Torbjørn Omland, MD, PhD

Victoria Vinje, MD

Jürgen Geisler, MD, PhD

Evandro F Fang, PhD

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.

Double-blind, randomised, placebo-controlled

The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.

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

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

Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses)

Change in transverse relaxation time (T2) measured by CMR

Change in longitudinal relaxation time (T1) measured by CMR

Change in left ventricular diastolic function as measured by echocardiography

Change in the aortic pulse wave velocity measured by CMR

Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP)

Chance in circulating cardiac myosin binding protein C (cMyC)

Change in circulating creatine kinase (CK)

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.

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.

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).

Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization to end of blinded therapy.

From randomization to the end of blinded therapy:

Change in LVEF, as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global circumferential strain (GCS) and GLS, as determined by CMR

From randomization to the end of blinded therapy:

Change in left ventricular end-systolic volume measured by CMR

From randomization to the end of blinded therapy:

Change in circulating hs-cTnT

From randomization to the end of blinded therapy:

Change in circulating hs-cTnI

From randomization to the end of blinded therapy:

Change in distance in meters during 6-minute walk test

From randomization to the end of blinded therapy:

Change in force generated by handgrip strength test

ChromaDex, Inc.

Norwegian Cancer Society

Norwegian Breast Cancer Association

Helse Sor-Ost

University Hospital, Akershus

Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Recurrence

Peripheral Nervous System Diseases

Head and Neck Neoplasms

Endometrial Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Neuromuscular Diseases

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Donna L Hammond, PhD

Alexandra Thomas, MD

The purpose of this single-arm phase II trial is to determine whether nicotinamide riboside (NIAGEN®) prevents the progression of peripheral sensory neuropathy in patients receiving infusions of paclitaxel or nab-paclitaxel for the treatment of metastatic breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, fallopian tube cancer or metastatic head and neck cancer.

Peripheral neuropathies are a dose-limiting, disabling, and debilitating side effect of virtually every known class of chemotherapeutic agent, and are referred to as chemotherapy-induced peripheral neuropathies (CIPN) (Seretny et al., 2014). The incidence and severity of CIPN increase as the cumulative dose, frequency of administration, and the number of therapeutic cycles increase. As many as 68% of patients have CIPN when assessed within 30 days of completing treatment. Patients experience paresthesias, dysesthesias (an unpleasant abnormal sensation, whether spontaneous or evoked), hyperalgesia (increased pain from a stimulus that normally provokes pain), allodynia (pain due to a stimulus that does not normally provoke pain), numbness or loss of sensation, or ongoing pain that is burning, lancinating or electric shock-like in nature. CIPN can seriously diminish a patient's quality of life, and can interfere with self-care and activities of daily living. The severity of CIPN may also necessitate reducing the dose of chemotherapeutic agent, delaying the next cycle of chemotherapy, or terminating treatment entirely (Argyriou et al., 2012; Argyriou et al., 2014; Miltenburg et al., 2014; Park et al., 2013).

Nicotinamide adenine dinucleotide (NAD+) is an essential redox coenzyme required for cell viability, basic bioenergetics, and fast axonal transport (Yang and Sauve, 2016). It plays an important role in protection against axonal injury from either mechanical or neurotoxic injury (Araki et al., 2004; Sasaki et al., 2006; Sasaki et al., 2009; Gerdts et al., 2015; Khan et al., 2014; Conforti et al., 2014; Di Stefano et al., 2015). Nicotinamide riboside (NIAGEN®) is a form of vitamin B3 and a precursor in the pathway for synthesis of NAD+ (Bieganowski et al., 2004; Trammell et al., 2016; Chi and Sauve, 2013). Oral administration of NIAGEN® increases levels of NAD+ in the blood, liver, skeletal muscle, and other tissues (Canto et al., 2012; Hamity et al, 2017; Airhart et al., 2017; Martens et al., 2018).

NIAGEN®) has been reported to prevent tactile hypersensitivity and blunt the affective dimension of nociception in a rat model of CIPN (Hamity et al., 2017) It also prevents signs of peripheral neuropathy in a mouse model of diabetes (Trammell et al., 2016) The proposed single-arm pilot phase II study will examine whether daily dosing with NIAGEN®) can prevent the progression of CIPN in persons with stage IV breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, or fallopian tube cancer receiving once weekly infusions of paclitaxel for 12 weeks.

In this study, persons with metastatic breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer who are receiving weekly infusions of paclitaxel or nab-paclitaxel and anticipated to survive for at least 3 months will be offered the opportunity to enroll in this study when they develop a peripheral neuropathy of at least grade 1. Persons with peripheral neuropathy of no greater than a grade 2 from prior therapy may also enroll in this study if they are receiving weekly infusions of paclitaxel or nab-paclitaxel. Upon enrollment, health care providers will review the overall severity of the participant's neuropathy and assign a baseline grade. Participants will also complete two short questionnaires that will more specifically score how the peripheral neuropathy interferes with daily functions of living. A small sample of blood will be taken at the completion of the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel. The participant will then be sent home with capsules of NIAGEN® to take twice daily. Each week upon return to the clinic a small sample of blood will be taken before the infusion of paclitaxel to measure biomarkers for NIAGEN®, and other samples of blood will be taken to evaluate clinical chemistries, kidney, and liver function. Another sample of blood will be obtained after the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel or nab-paclitaxel. The health care provider will meet with the patient each week to score the overall severity of the peripheral neuropathy, and the participant will answer another questionnaire with more specific questions. Once a month, the participant will be asked to fill out a second questionnaire. Participants will take 300 mg/day NIAGEN® in the first week and 1000 mg/day in the subsequent 11 weeks. The study will conclude one week after the 12th infusion of paclitaxel or nab-paclitaxel. Health care providers will contact the participant at various times up to 6 months to monitor their status.

Beginning with completion of the trial by the 10th participant and continuing with each subsequent participant up to 39, we will use a Bayesian statistical approach (Lee and Liu, 2008; i.e. predictive probability) to determine whether NIAGEN® has prevented a worsening of the peripheral neuropathy. This approach we let us make an early determination of futility. We will also determine whether NIAGEN® has decreased the need to delay or diminish the doses of paclitaxel or nab-paclitaxel due to severity of the peripheral neuropathy. The results of this trial will inform the design of a subsequent randomized, placebo-controlled, blinded clinical trial.

All subjects with stage IV breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer will receive 300 mg NIAGEN®) daily for one week followed by dose escalation to 1000 mg daily for 11 weeks upon reporting the development of grade 1 sensory neuropathy. Those presenting with a residual sensory neuropathy of ≤ 2 as a result of prior chemotherapy will also be enrolled.

NR in Chemo-induced Peripheral Neuropathy

Nicotinamide Riboside (NR) in Paclitaxel-induced Peripheral Neuropathy

All of the individual participant data collected during the trial, after de-identification, will be shared with researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. The IPD will be available to sharing immediately after publication and ending 5 years after article publication

Exploratory analysis of ability of the clinical version of the Total Neuropathy Score questionnaire to detect changes in CIPN severity over time. Unlike the CTCAE or the FACT\&GOG-NTX questionnaires, the TNS is a patient reported outcome measure. HIghest score (worse neuropathy is 24, lowest score is 0. Outcome assessed difference between end of treatment and screening. A positive number indicates improvement in neuropathy

The primary outcome variable is defined as no worsening of the grade of peripheral sensory neuropathy as scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines. Per the CTCAE a score of 1 would be assigned in the instance of parethesias or a loss of deep tendon reflexes. A score of 2 would be assigned in the instance of moderate symptoms that limit instrumental activities of daily living. A score of 3 would be assigned in the instance of severe symptoms that limit self-care activities of daily living. Because the outcome measure is defined as no worsening of the grade, it was recorded as either "yes"( i.e. it worsened) or "no" (i.e. it did not worsen).

Quantitate the percentage of patients that experience a dose reduction of paclitaxel or nab-paclitaxel therapy due to neuropathy.

Count the number of (i.e. the incidence) of dose reduction events due to neuropathy (each occasion of dose reduction is a separate event);

Quantitate the total cumulative dose of paclitaxel administered over the 12 weeks.

Difference in Score on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity questionnaire at the end of treatment; i.e. Score at screening - score at end of treatment. This questionnaire asks 11 questions that are specific to chemotherapy-induced peripheral neuropathies. Maximum score is 44, minimum score is 0. Positive differences indicate a decrease in neuropathy. Negative differences indicate a worsening of neuropathy. Zero means unchanged.

National Cancer Institute (NCI)

Donna Hammond, PhD

Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Nicotinamide Riboside: Capsule

NIAGEN®)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Plasma sample obtained before NIAGEN treatment begun

NAD concentration plasma levels

Plasma samples obtained before NIAGEN treatment begun

1-methyl-nicotinamide plasma levels

Plasma sample obtained 10-20 min after taxane infusion ended

one sample not submitted due to subject testing COVID positive and withdrawing from study

paclitaxel plasma levels

This trial was limited to a non-curative population of women receiving taxane chemotherapy without added platinum-based agents. Difficulty in recruiting this small population led to eventual termination of the trial. Dose escalation to 1000 mg/day did not occur for any subject due to physician concerns that subjects were not tolerating the 300 mg dose well.

Donna L. Hammond, Ph.D Professor

Data are reported for the 4 subjects who took at least one dose of NIAGEN. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~14 weeks). If a patient withdrew before completing 12 weeks of treatment, the end of treatment was designated as one week after withdrawal from the study. The longest that any participant was on NIAGEN was three weeks. Therefore, the time frame of the study has been adjusted to \~4 weeks.

Number of Participants With No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That subject patient received only 2 doses of taxane over a period of 3 weeks. No patient completed the full 12 weeks of the trial. Therefore, the time frame of the study has been adjusted from the originally envisioned 12 weeks to \~3 weeks.

Percentage of Patients in Which Dose of Paclitaxel or Nab-Paclitaxel is Reduced Due to CIPN

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That patient received only 2 doses of taxane over a period of 3 weeks. The original aim was to assess dose reduction over the 12 weeks of paclitaxel treatment, but no patient completed the 12 weeks of treatment. As the longest that any patient was on NIAGEN was 3 weeks, the time frame has been adjusted accordingly.

Number of Dose Reduction Events

Data are reported for the 1 subject who received taxane infusions after starting NIAGEN treatment. They received 2 infusions over a period of three weeks of NIAGEN treatment.

Total Dose of Paclitaxel Administered

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the FACT questionnaire. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~ 14 weeks). If a patient withdrew before then, the end of treatment was designated as one week after withdrawal. Unfortunately, the longest that any patient was on NIAGEN was three weeks. Therefore, the time frame has been adjusted to \~4 weeks.

Difference in Score Between Baseline and End of Treatment for the FACT&GOG-NTX Subscale .

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the TNS evaluation. No patient completed the full 12 weeks of the trial. Therefore, the measure was made at end of treatment, which was designated as one week after they ceased NIAGEN treatment. The longest any one patient was on NIAGEN was three weeks. Hence the time frame was adjusted to 4 weeks.

Difference in Total Neuropathy Score Between Screening and End of Treatment

Paclitaxel levels in plasma were measured \~30 min after each infusion of taxane. This was undertaken to ascertain whether NIAGEN altered plasma levels of paclitaxel because increases or decreases in plasma levels of paclitaxel by itself could lead to an apparent worsening or improvement, respectively, in CIPN and confound interpretation of NIAGEN's effect.

Data are reported for three subjects in which paclitaxel levels were obtained before NIAGEN and after NIAGEN treatment, which ranged from one to three weeks. The plasma concentration for the last blood sample obtained after NIAGEN treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients	NCT05732051	Breast Cancer Metastatic Brea... Cancer Therapy-... Cardiotoxicity Heart Failure	Nicotinamide Ri... Placebo	18 Years -	University Hospital, Akershus
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa

Spots Global Cancer Trial Database for niagen

Every month we try and update this database with for niagen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for niagen

Every month we try and update this database with for niagen cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for niagen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.