Clinical trial NCT03038516: 'Palliative-D' Vitamin D to Palliative Cancer Patients
Official title: 'Palliative-D' Vitamin D Supplementation to Palliative Cancer Patients - A Double Blind, Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vitamin D Deficiency
Lead sponsor: Region Stockholm
Sponsor class: OTHER_GOV
First posted: 2017-01-31
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients can decrease opioid consumption, fatigue and infectious burden and increase quality of life.

Detailed description: PROTOCOL IDENTITY AND OBJECTIVES: EudraCT Number 2017-000268-14 Protocol Title: Vitamin D supplementation to palliative cancer patients - A double blind, randomised controlled trial. Acronym: "Palliative-D" Trial Objectives: To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients can decrease opioid consumption, fatigue and infectious burden and increase quality of life.

INVESTIGATIONAL MEDICINAL PRODUCTS (IMP): Test ProductDetremin, MA holder Renapharma; Pharmaceutical Form: Oil Route of Administration: Oral route

METHODOLOGY Trial Design: Double-blind, parallel randomised and placebo controlled trial Dose/Duration 4000 IU/day for 12 weeks

Primary Endpoint:

The decline of opioid-consumption during 12 weeks in the vitamin D group compared to the placebo group, based on 3 measurements with 4 weeks intervals.

Secondary end Points:

1. Decline in antibiotic consumption
2. Improvement in quality of life
3. Improvement in fatigue
4. Vitamin D levels in serum after 12 weeks
5. Association between opioid dose and genetic polymorphism in genes involved in the effect and metabolism of vitamin D in the body.

Efficacy Parameters:

Opioid dose, translated to fentanyl per hour measured at baseline and at week 4,8 and 12.

Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks measured at baseline and at week 4, 8 and 12.

Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. Fatigue measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. 25-hydroxyvitamin D levels in blood at baseline and after 12 weeks. ESAS (Edmonton Symptom Assessment Scale ) measured at baseline and at week 4, 8 and 12.

Safety Parameters: S-calcium will be controlled in all subjects at baseline, at week 4, 8 and 12 and U-calcium in selected cases Power: The least clinically meaningful effect is estimated to be a 20% decline in opioid dose compared to the placebo. To obtain this result with 80% power the number of patients is estimated to be 127 in each arm i.e. 254 patients in total. This includes a drop-out of 25% per group.

Statistical Analyse plan: The primary endpoint will be analysed using linear regression, using bias corrected and accelerated bootstrap confidence intervals, while controlling for baseline measure of opioid dose (similar to ANCOVA). Adjustment for other background variables - such as vitamin D-level at baseline, gender and age - will be made in a secondary analysis to gain efficiency. The continuous secondary endpoints will be analysed using the same method as the primary endpoint .

POPULATION OF TRIAL SUBJECTS Number of Subjects: 254 (127 vitamin D and 127 placebo) Description of Trial Subjects: Palliative Cancer Patients (any cancer form) with a life expectancy of more than 3 months.

TRIAL TIMETABLE First Subject In Aug 2017 Last Subject In Sept 2019 (25 months to include participants) Last Subject Out Dec 2019 End of intervention Dec 2019 End of follow up Dec2019 End of Trial: Dec 2020

Eligibility criteria: Inclusion Criteria:

1. Patients admitted to ASIH Stockholm Södra or Stockholms Sjukhem.
2. Incurable cancer patients with any type of cancer. They could have ongoing oncological treatment but only with palliative intention. No patients with ongoing oncological treatment with curative intended treated will be included.
3. The life expectancy should be at least 3 months according to the clinical assessment of the study physician at the screening visit.
4. The patient should have no cognitive failure, being able to comprehend oral and written information about the study.
5. 25 OHD \< 50 nmol/L.
6. Men and women aged ≥18
7. Signed 'informed consent'

Exclusion Criteria:

1. Ongoing vitamin D supplementation at the time for inclusion.
2. Serum level of 25-OH vitamin D3 \>50 nmol/L
3. Known sarkoidosis
4. Treatment with tiazides or digoxin or digitoxin
5. Primary hyperparathyroidism
6. Hypercalcaemia (verified by a laboratory result younger than 2 month)
7. Plans to leave the Stockholm county within 12 weeks of inclusion
8. History of kidney stones
9. Taking part of another clinical study involving drugs
10. Hypersensitivity to cholecalciferol and/or any of the excipients
11. Other criteria that could jeopardize the study or its intention as judged by the investigator
12. Not being able to perform EORTC-QLQ-C15-PAL or ESAS

Primary outcomes:
measure: Change in opioid dose during 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Antibiotic Consumption during 12 weeks
timeFrame: 12weeks
measure: Change in Quality of life after 12 weeks
timeFrame: 12 weeks
measure: Change in Fatigue after12 weeks
timeFrame: 12 weeks
measure: Change in 25-hydroxyvitamin D levels after 12 weeks
timeFrame: 12 weeks
measure: Change in Symptom burden during 12 weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Solna
country: Sweden
facility: ASIH Stockholm Norr
state: Stockholm
city: Stockholm
country: Sweden
facility: Stockholms Sjukhem ASIH
city: Älvsjö
country: Sweden
facility: ASIH Stockholm Södra
Study officials:
affiliation: Stockholm Läns Landsting
name: Linda Björkhem-Bergman, Assoc Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klasson C, Helde-Frankling M, Sandberg C, Nordstrom M, Lundh-Hagelin C, Bjorkhem-Bergman L. Vitamin D and Fatigue in Palliative Cancer: A Cross-Sectional Study of Sex Difference in Baseline Data from the Palliative D Cohort. J Palliat Med. 2021 Mar;24(3):433-437. doi: 10.1089/jpm.2020.0283. Epub 2020 Sep 16.