Vitamin D Supplementation in Individuals With a Chronic Spinal Cord Injury

Study Overview
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Brief Summary
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The main objective of this placebo-controlled randomized double-blinded study is to investigate the effect of vitamin D supplementation on vitamin D status (25(OH)D concentration in the blood) among individuals with a chronic spinal cord injury (SCI). Further, the effects of vitamin D supplementation on several other parameters (e.g. bone density and mood) are investigated, which could reveal positive secondary effects of supplementation that are especially relevant for clinical practice.

Detailed Description
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The purpose of this study is to evaluate the influence of vitamin D supplementation among individuals with chronic SCI. The primary aim is to study whether different dosages (24'000 IU/month or 48'000 IU/month) of vitamin D supplementation over 12 months will lead to differences in vitamin D status as well as differences in several other outcomes. The use of a placebo group supports the evaluation of dose-response effects of vitamin D supplementation on the primary outcome (vitamin D status) and secondary outcomes (including bone density and mood) that are not only supported by randomized controlled trial standards but also informative in clinical practice.

Official Title
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Vitamin D Supplementation in Individuals With a Chronic Spinal Cord Injury - a Placebo-controlled Randomized Double-blinded Study

Conditions
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Spinal Cord Injuries, Vitamin D Deficiency

Intervention / Treatment
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* Drug: Cholecalciferol (Vitamin D3)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent to the present study as documented by a signature Chronic (> 3 years) traumatic or non-traumatic spinal cord injury with a sub-C4-level lesion Wheelchair dependency during activities of daily living vitamin D status <75nmol/L Exclusion Criteria: Contraindications to the investigational product Clinically relevant disorders, Pressure ulcer grade 3 or 4 Pregnancy, breastfeeding Vitamin D supplementation (> 400 IU/day) within the last 12 months Visiting a country with increased sun exposure (below the 37th parallel north) within the last month before study enrolment or during the study Fractures in both arms and/or both legs within the last five years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants having a vitamin D status ≤ 75 nmol/L at baseline, will be randomly assigned to one of the three intervention groups.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>One vial with 600 µg cholecalciferol (corresponding to a total of 24'000 IU vitamin D) and one vial with placebo every month. | Drug: Cholecalciferol (Vitamin D3)<br>* Vi-De 3® Monthly Dose from Dr. Wild & Co. AG (Muttenz, Switzerland) is a commercially available vitamin D3 supplement.<br>* Other names: Vi-De 3® Monthly Dose;Other: Placebo<br>* A placebo will be produced, consisting of the same ethanol solution as Vi-De 3® Monthly Dose, but without cholecalciferol.<br>|
| Experimental: High dose<br>Two vials with 600 µg cholecalciferol each (corresponding to a total of 48'000 IU vitamin D) every month. | Drug: Cholecalciferol (Vitamin D3)<br>* Vi-De 3® Monthly Dose from Dr. Wild & Co. AG (Muttenz, Switzerland) is a commercially available vitamin D3 supplement.<br>* Other names: Vi-De 3® Monthly Dose;|
| Placebo Comparator: Placebo<br>Two vials with a placebo every month. | Other: Placebo<br>* A placebo will be produced, consisting of the same ethanol solution as Vi-De 3® Monthly Dose, but without cholecalciferol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D status | Serum levels of 25(OH)D in nmol/L | 0 to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone density | Measurements of the forearm (radius), hip (femoral neck) and knee (distal femur and proximal tibia) will be performed using dual-energy X-ray absorptiometry (DXA) scans. T-values will be reported. | At baseline and after 12 months | 
| Mood | Assessed by the Hospital Anxiety and Depression Scale (HADS) questionnaire, using a 4-step scale (1-4) with a total range of 14-56 and higher scores indicating worse outcomes. | At 0, 3, 6, 9, 12 months | 
| Fatigue | Assessed by the Fatigue Severity Scale (FSS) questionnaire, using a 8-step scale (1-7) with total range 9-63 and higher scores indicating worse outcomes. | At 0, 3, 6, 9, 12 months | 
| Chronic pain | The occurrence of pain since the last visit is assessed by one question of the SCI Secondary Conditions Scale (Kalpakjian, Scelza et al. 2007), providing a five-step rating (0-4) with a higher score indicating a worse outcome. | At 0, 3, 6, 9, 12 months | 
| Recent pain | The occurrence, kind, location and interference of pain during the last week is assessed using questions of the adapted version of the International SCI Pain Basic Data Set (Widerström-Noga, Biering-Sørensen et al. 2008). The interference of pain is measured on a 11-step scale (0-10), with total range 0-30 and higher scores indicating worse outcomes. | At 0, 3, 6, 9, 12 months | 
| Pressure injuries | The occurrence, localization and severity of pressure injuries is assessed by the exact questions of the first-wave questionnaire of the Swiss Spinal Cord Injury Cohort Study (SwiSCI) survey (Post, Brinkhof et al. 2011, Brinkhof, Fekete et al. 2016). The severity or grade is assessed using the European and US National Pressure Ulcer Advisory panels' (EPUAP-NPUAP) classification (National Pressure Ulcer Advisory Panel and Alliance. 2014), using a 4 point scale (1-4) and higher grades indicating worse outcomes. | At 0, 3, 6, 9, 12 months |