The purpose of this randomized, double-blind, placebo-controlled, parallel group phase II trial is to determine whether nicotinamide riboside (NIAGEN®, NR) can ameliorate persistent peripheral neuropathy in cancer survivors who have completed chemotherapy with taxane or platinum-complex compounds between 1 and 12 months earlier.
Patients who have been declared to be in complete remission after treatment of their cancer with either taxane or platinum-based compounds and who have persistent neuropathy will be randomized to receive either placebo or NIAGEN capsules daily for 84 days. On enrollment, subjects will complete several questionnaires characterizing the type and severity of their neuropathy. Their fifth finger will be scanned to determine the density of sensory afferents in the skin, and a skin biopsy will be taken above the ankle for histological analysis of nerve fiber density. Blood samples will be drawn for baseline measures of NAD+ levels, and clinical chemistries and indices of liver and kidney function. Subjects will be asked to return every two weeks to complete the questionnaires, and blood will be drawn to measure biomarkers of NIAGEN consumption. Blood will be drawn at visits on days 28, 56, and 84 for clinical chemistries and measures of liver and kidney function. At visits on day 42 and 84, additional measures of density of nerve fibers in the hand and leg will be made. The last treatment day will be day 84, at which time all measures will be redetermined. A follow-up period of 3 months is planned at which time all measures will be conducted once again to determine if any alleviation of the chemotherapy has persisted after treatment ended. Patients enrolled in this study will receive standard of care treatment by their oncologists, which includes computed tomography, magnetic resonance or ultrasound scans every three months as surveillance for cancer re-occurrence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
48
Daily oral ingestion of 1 g/day NIAGEN in capsule form for 84 days; two capsules in the a.m. and two capsules in the p.m.
Daily oral ingestion of placebo in capsule form for 84 days; two capsules in the a.m. and two capsules in the p.m.
Donna Hammond
Iowa City, Iowa, United States
Score on Sensory Subscale of Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy (QLQ-CIPN20)
Change in score from baseline to end of treatment at 84 days. The Quality of Life Questionnaire for Chemotherapy-induced Peripheral Neuropathy (20 questions) or QLQ-CIPN20 yields scores of 1-4 (Likert scale) for 9 sensory, 8 motor, and 3 autonomic sequelae of chemotherapy. The minimum score for the sensory subscale is 9 and the maximum possible score is 36. The higher the score, the worse the signs and symptoms. The raw score can, at the investigator's discretion, be linearly transformed to a 0-100 scale, where higher numbers represent worse symptoms. Recent publications call the validity of the autonomic scale into question, and it is not being used in this study.
Time frame: 84 days
Score on Motor Subscale of Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy (QLQ-CIPN20)
Change in score from baseline to end of treatment at 84 days. The Quality of Life Questionnaire for Chemotherapy-induced Peripheral Neuropathy (20 questions) or QLQ-CIPN20 yields scores of 1-4 (Likert scale) for 9 sensory, 8 motor, and 3 autonomic sequelae of chemotherapy. The minimum score for the motor subscale is 8 and the maximum possible score is 32. The higher the score, the worse the signs and symptoms. The raw score can, at the investigator's discretion, be linearly transformed to a 0-100 scale, where higher numbers represent worse symptoms. Recent publications call the validity of the autonomic scale into question, and it is not being used in this study.
Time frame: 84 days
Total Neuropathy Score - clinical questionnaire
Change in score from baseline to end of treatment at 84 days. The clinical version of the Total Neuropathy Score yields scores of 0-4 on 6 items (sensory symptoms, motor symptoms, pin sensibility, vibration sensibility, strength and deep tendon reflex). The minimum possible score is 0 and the maximum possible score is 30. Scores for each of the six items are summed to yield a single total score. The higher the score, the worse the outcome.
Time frame: 84 days
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Intraepidermal Nerve Fiber Density
Change in score from baseline to end of treatment at 84 days
Time frame: 84 days