Vitamin D for Muscle Metabolic Function in Cancer Cachexia

NCT03144128 | Completed DMC

• 2 other identifiers: MCC-15-LUN-102MCC Protocol #15-1024-F1V
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is aimed at examining mitochondrial function as a potential target of action of vitamin D on muscle metabolism, size, and strength in preventing the progression of cachexia. This is the first clinical trial designed to understand the effects of vitamin D on muscle metabolic dynamics driving dysfunction in cachectic muscle. Our preliminary data suggest that vitamin D promotes lipid partitioning and muscle metabolic function, which the investigators hypothesize, will mitigate cachexia via improved muscle health and quality that translates into reduced fatigue, and improved patient resilience to multimodal cancer therapy.

Conditions

Cancer Cachexia; Vitamin D Deficiency

Keywords

vitamin D; muscle; metabolism; cancer cachexia

Outcome Measures

Primary Outcomes (4)

• Non-invasive quantification of muscle lipid distribution

  MRI/MRS

  Change between Week 0 and Week 12

• Local muscle oxygen consumption

  Near Infrared Spectroscopy + Diffuse Correlation Spectroscopy measures will be combined to assess changes in local muscle tissue oxygen consumption (VO2 measure)

  Change between Week 0 and Week 12

• Muscle Mass

  MRI

  Change between Week 0 and Week 12

• Muscle Strength

  Maximal voluntary contractions and 1-Repetition Maximum will be aggregated to to provide a comprehensive assessment of muscle strength

  Change between Week 0, Week 6, Week 12

Secondary Outcomes (6)

• Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo

  Experiments will be conducted from tissue collected at week 12 study biopsy

• Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo

  Experiments will be conducted from tissue collected at week 12 study biopsy

• Stable Isotope-Resolved Metabolomics to describe Fatty Acid Metabolism in relationship to other fuel substrates in Fresh Muscle Fibers ex vivo

  Experiments will be conducted from live tissue collected at week 12 study biopsy

• Utilize cell culture experimentation to understand anabolic signaling in response to vitamin D with or without fiber stretch.

  Experiments will be conducted from tissue collected at week 12 study biopsy

• Utilize cell culture experimentation to measure mitochondrial activity in response to vitamin D with or without fiber stretch.

  Experiments will be conducted from tissue collected at week 12 study biopsy

Study Arms (2)

Control (Ctl)

PLACEBO COMPARATOR

Standard of Care resistance exercise and timed protein supplementation with placebo capsule daily for 12 weeks

Dietary Supplement: Placebo

Vitamin D

EXPERIMENTAL

Standard of Care resistance exercise and timed protein supplementation with 5,000IU vitamin D supplementation daily for 12 weeks

Dietary Supplement: Vitamin D

Interventions

Vitamin D DIETARY_SUPPLEMENT

5,000IU vitamin D given daily for 12 weeks

Vitamin D

Placebo DIETARY_SUPPLEMENT

Placebo capsules given daily for 12 weeks

Control (Ctl)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed stage II-IV lung cancer and be planned for definitive non-surgical therapy.
• Patients may have a history of prior malignancy.
• Mild cancer cachexia, defined by the miniCASCO score of 0-25 points
• Vitamin D insufficiency, defined as 25(OH)D \< 32 ng/ml
• Aged 45 to 75 years. Stratified randomization by age
• ECOG performance status ≤ 2 (see Appendix A).
• Life expectancy of greater than 3 months
• Patients must have normal renal and liver function as defined below:
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Able to swallow thin liquids
• No uncontrolled illness including, but not limited to, any of the following:
• Ongoing or active serious infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Uncontrolled cardiac arrhythmia

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated brain metastasis are eligible for this trial, providing they have completed treatment at least one day prior to registration.
• History of allergic reactions to whey or milk proteins.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a history of calcium oxalate nephrolithiasis are excluded.
• Patients with a significant history of malabsorption (e.g. celiac sprue, short bowel syndrome, IBD or other, as determined by the treating physician) are excluded.
• Patients will not be eligible if actively receiving treatment for vitamin D deficiency and have had recent (3 month) history of vitamin D supplementation (\>1000 IU) or calcium supplementation (\>800mg).
• Patients will also be excluded if they report lower extremity (LE) surgery or injury to the LE in the past 3 months or a past medical history of primary hyperparathyroidism; or rhabdomyolysis.
• metal implants or other contraindications for the MRI;
• diabetes,
• advanced renal disease,
• uncontrolled hypertension;
• a vitamin D status (25(OH)D) of \> 32ng/mL.

Sponsors & Collaborators

• David Travis Thomas: lead

Study Sites (1)

Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Vitamin D Deficiency

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects receive exercise and protein supplementation. Participants, Investigators, Care Providers, and outcome assessors will be blinded to vitamin D vs. placebo capsule allocation
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective, double-blinded randomized controlled clinical trial

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: May 8, 2017
• Study Start: May 23, 2018
• Primary Completion: September 13, 2018
• Study Completion: September 13, 2018
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)