Vit D and Peripheral Neuropathy in Taxane Naive Patients

To evaluate the efficacy of vit D supplement in cancer patients which receive taxane drugs with vit D deficiency and complaining from Peripheral neuropathy

Study Overview

• Status: Not yet recruiting
• Conditions: Vitamin D Deficiency; Peripheral Neuropathy
• Intervention / Treatment: Drug: Vitamin D

Detailed Description

Taxanes are a class of chemotherapy agents that promote the polymerization of tubulin into highly stable, intracellular microtubules. These microtubules cause cell death by interfering with normal cell division. (1,2) The first taxane developed and tested in the field of oncology was paclitaxel.(3,4 )The introduction of paclitaxel to the armamentarium of oncologic therapy in the early 1990s had a great impact on the standard of care in lung carcinoma, breast carcinoma, ovarian carcinoma, and other solid tumors. Subsequent to this development, another taxane, docetaxel was introduced. (5,6) Unfortunately, taxane therapy is associated with side effects such as peripheral neuropathy, myelosuppression, arthralgias, myalgias, and skin reactions that may adversely affect patient-reported quality of life (QOL). Peripheral neuropathy in particular can be severe. This toxicity is cumulative across the course of therapy, can be a dose-limiting toxicity, and may lead to dose reduction or cessation of therapy. (7) Peripheral neuropathies encompass disorders of peripheral nerve cells and fibers which manifest secondary to a wide range of pathologies. These nerves include cranial nerves, spinal nerve roots & ganglia, nerve trunks & division, along with nerves of the autonomic nervous system. The most frequently encountered symptoms of peripheral neuropathy include numbness and paresthesias , pain, weakness, and loss of deep tendon reflexes may accompany these symptoms. (8) Vitamin D is a fat-soluble vitamin that plays an important role in calcium homeostasis and bone metabolism, vitamin-D deficiency is associated with osteoporosis, increased risk of falls and fragility fractures. Many conflicting recent studies are now showing an association between vitamin D deficiency and cancer, cardiovascular disease, diabetes, autoimmune diseases, and depression. (9) Initial supplementation for 8 weeks with Vitamin D3 either 6,000 IU daily or 50,000 IU weekly can be considered. Once the serum 25-hydroxyvitamin D level exceeds 30 ng/mL, a daily maintenance dose of 1,000 to 2,000 IU is recommended. A higher-dose initial supplementation with vitamin D3 at 10,000 IU daily may be needed in high-risk adults who are vitamin D deficient (African Americans, Hispanics, obese, taking certain medications, malabsorption syndrome). Once serum 25-hydroxyvitamin D level exceeds 30ng/mL, 3000 to 6000 IU/day maintenance dose is recommended.(10) A 2022 ASCO meeting abstract by Chen et al reported that patients with vitamin D deficiency had more paclitaxel-induced neuropathy than those with normal vitamin D blood concentrations. (11)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any cancer patient > 18 years old receive taxane treatment

Exclusion Criteria:

• Patient which receive any line of treatment cause Peripheral neuropathy before taxane.
• Chronic disease associated with neuropathy such as diabetes mellitus, Guillain-Barre syndrome and autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D supplement; Vitamin D supplement intake for 6 months	Drug: Vitamin D; vitamin D supplement in cancer patients which receive taxane drugs with vit D deficiency and complaining from Peripheral neuropathy.
Placebo Comparator: Placebo group; Group with no vitamin D supplement treatment	Drug: Vitamin D; vitamin D supplement in cancer patients which receive taxane drugs with vit D deficiency and complaining from Peripheral neuropathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grades of neuropathy according to the World Health Organization rating scale	Grade 0 corresponds to no symptoms of neuropathy, grade 1 corresponds to paresthesias (a tingling, tickling or prickling sensation) and/or decreased tendon reflexes, grade 2 corresponds to severe paresthesias and/or mild weakness, grade 3 corresponds to intolerable paresthesias and /or marked motor loss, Grade 4 Paralysis	after 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Toronto Clinical Neuropathy Score (TCNS)	Valid and reliable scale for use in common non-diabetic polyneuropathies. Primarily for the feet. Most of the testing is done on or near the toes. Light touch testing is done with a 10 gm monofilament on the dorsum of the large toe	after 6 months

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2023
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Nutrition Disorders; Neuromuscular Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Peripheral Nervous System Diseases; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: 357167

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No