The Role of Vitamin D3 Supplementation in Advanced Cancer Patients With Pain

NCT05450419 | Unknown DMC

• 1 other identifier: 202100708A3
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Many patients with cancer have insufficient vitamin D levels, and low vitamin D levels are associated with increased 'all-cause mortality' and especially mortality due to cancer. Vitamin D has anti-cancer effects, including anti-proliferation, anti-angiogenesis, and anti-inflammation. Besides, low vitamin D levels are associated with higher opioid dose usage, fatigue, and impaired quality of life in palliative cancer patients. Therefore, patients with low vitamin D levels needs instant vitamin D supplement with "stoss therapy" which is single high dose vitamin D with maintenance dose by enteral route. The stoss therapy has been applied in many fields, including neonatal, diabetes, hemodialysis, heart failure, osteoporosis. In critically ill patients, such as surgical, medical, burn intensive unit admission patients, high dose vitamin D supplement was associated lower mortality amount the vitamin D deficiency patients. This study aims for evaluating the effects of enteral high dose vitamin D supplement on advanced cancer patients with pain, serum concentration changes of vitamin D, quality of life, symptom burden, and analyze its correlation with inflammation, immune and nutritional markers.

Conditions

Vitamin D3; Advanced Cancer; Pain Cancer

Keywords

Vitamin D3; Pain; Advanced cancer

Outcome Measures

Primary Outcomes (3)

• Oral morphine dose change

  Change of equivalent oral morphine dose

  Week 1 to Week 5

• Pain score assessment

  Visual Analogue Scale pain scale 0 to 10.

  Week 1 to Week 5

• Total 25(OH)D levels

  Achieved 25(OH)D levels of at least 30 ng/mL

  Week 1 to Week 5

Secondary Outcomes (12)

• Quality of life changes

  Week 1 to Week 5

• Symptom burden

  Week 1 to Week 5

• Serum concentration changes of 25(OH)D

  Week 1 to Week 5

• Albumin

  Week 1 to Week 5

• Transferrin

  Week 1 to Week 5

Study Arms (2)

Vitamin D3

ACTIVE COMPARATOR

Patient received enteral supplementation of 576,000 IU vitamin D3 on week 1, then enteral supplementation of 72,000 IU vitamin D3 on week 2, week 3 \& week 4.

Dietary Supplement: Vitamin D3

Placebo

PLACEBO COMPARATOR

Patient received enteral supplementation of placebo on week 1, then enteral supplementation of placebo on week 2, week 3 \& week 4.

Dietary Supplement: placebo

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

8pc (576,000 IU/40ml) vitamin D3 on week 1, then 1pc (72,000 IU/5ml) vitamin D3 on week 2, week 3 \& week 4.

Vitamin D3

placebo DIETARY_SUPPLEMENT

8pc placebo on week 1, then 1pc placebo on week 2, week 3 \& week 4.

Placebo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent/metastatic cancer patients scheduled to receive 2nd or later lines of systemic chemotherapy with no curative intent.
• Oral equivalent morphine of at least 60 mg/day.
• Visual analog scale (VAS) of pain ≥ 3.
• Age between 20-80 years old.
• Life expectancy should be at least 3 months according to the clinical assessment of physician.
• The patient should have no cognitive dysfunction and able to answer questionnaire.

You may not qualify if:

• Abnormal gastrointestinal function: patients could not tolerate enteral feeding.
• Current use of supplemental vitamin D or supplements containing vitamin D beyond the protocol.
• Pre-existing hypercalcemia (defined as baseline serum calcium above the institutional upper limit of normal (ULN), corrected for albumin level if albumin is not within institutional limits of normal.
• Concomitant drugs which may interfere with study evaluation:
• Steroids: treated with steroid for medical purpose such as autoimmune disease (i.e, SLE) for long term; Short term use of corticosteroids as anti-emetic therapy for chemotherapy is permitted.
• Astragalus Polysaccharides (PG2).
• Chemo young oral solution.
• Heart failure New York Heart Association (NYHA) Class IV.
• Impaired liver function (serum total bilirubin \> 3x ULN, alanine amino transferase (ALT) or aspartate amino transferase (AST) \> 5 x ULN).
• Impaired renal function: serum creatinine \> 2 x ULN.
• Inadequate bone marrow function (absolute neutrophil count \< 1,500/mm\^3 (\< 1.5 x 10\^9/L), platelets \< 75,000 / mm\^3 (\< 75 x 10\^9/L) and hemoglobin \< 10 g/dL).
• Uncontrolled infection
• History of primary hyperparathyroidism
• History of nephrolithiasis
• Thiazides or digoxin use

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital

Keelung, 204, Taiwan

RECRUITING

Related Publications (9)

• Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011 Jun;7(6):337-45. doi: 10.1038/nrendo.2010.226. Epub 2011 Jan 25.

  PMID: 21263449 BACKGROUND

• Bruns H, Buttner M, Fabri M, Mougiakakos D, Bittenbring JT, Hoffmann MH, Beier F, Pasemann S, Jitschin R, Hofmann AD, Neumann F, Daniel C, Maurberger A, Kempkes B, Amann K, Mackensen A, Gerbitz A. Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma. Sci Transl Med. 2015 Apr 8;7(282):282ra47. doi: 10.1126/scitranslmed.aaa3230.

  PMID: 25855493 BACKGROUND

• Dev R, Del Fabbro E, Schwartz GG, Hui D, Palla SL, Gutierrez N, Bruera E. Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia. Oncologist. 2011;16(11):1637-41. doi: 10.1634/theoncologist.2011-0151. Epub 2011 Sep 30.

  PMID: 21964001 BACKGROUND

• Spedding S, Vanlint S, Morris H, Scragg R. Does vitamin D sufficiency equate to a single serum 25-hydroxyvitamin D level or are different levels required for non-skeletal diseases? Nutrients. 2013 Dec 16;5(12):5127-39. doi: 10.3390/nu5125127.

  PMID: 24352091 BACKGROUND

• Bergman P, Sperneder S, Hoijer J, Bergqvist J, Bjorkhem-Bergman L. Low vitamin D levels are associated with higher opioid dose in palliative cancer patients--results from an observational study in Sweden. PLoS One. 2015 May 27;10(5):e0128223. doi: 10.1371/journal.pone.0128223. eCollection 2015.

  PMID: 26018761 BACKGROUND

• Martinez-Alonso M, Dusso A, Ariza G, Nabal M. Vitamin D deficiency and its association with fatigue and quality of life in advanced cancer patients under palliative care: A cross-sectional study. Palliat Med. 2016 Jan;30(1):89-96. doi: 10.1177/0269216315601954. Epub 2015 Aug 27.

  PMID: 26315460 BACKGROUND

• Helde-Frankling M, Hoijer J, Bergqvist J, Bjorkhem-Bergman L. Vitamin D supplementation to palliative cancer patients shows positive effects on pain and infections-Results from a matched case-control study. PLoS One. 2017 Aug 31;12(8):e0184208. doi: 10.1371/journal.pone.0184208. eCollection 2017.

  PMID: 28859173 BACKGROUND

• Ng K, Nimeiri HS, McCleary NJ, Abrams TA, Yurgelun MB, Cleary JM, Rubinson DA, Schrag D, Miksad R, Bullock AJ, Allen J, Zuckerman D, Chan E, Chan JA, Wolpin BM, Constantine M, Weckstein DJ, Faggen MA, Thomas CA, Kournioti C, Yuan C, Ganser C, Wilkinson B, Mackintosh C, Zheng H, Hollis BW, Meyerhardt JA, Fuchs CS. Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial. JAMA. 2019 Apr 9;321(14):1370-1379. doi: 10.1001/jama.2019.2402.

  PMID: 30964527 BACKGROUND

• Han JE, Jones JL, Tangpricha V, Brown MA, Brown LAS, Hao L, Hebbar G, Lee MJ, Liu S, Ziegler TR, Martin GS. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. J Clin Transl Endocrinol. 2016 Jun;4:59-65. doi: 10.1016/j.jcte.2016.04.004. Epub 2016 May 5.

  PMID: 27419080 BACKGROUND

MeSH Terms

Conditions

Cancer Pain; Pain

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Hang Huong Ling, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li-Ting Lian

CONTACT

+886-224329292; liting@cgmh.org.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 8, 2022
• Study Start: July 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)