Dose Finding Study in Physically Frail Elderly to Measure 25(OH) Vitamin D Levels After Supplementation With Hy.D Calcifediol 25 SD/S and Vitamin D3

Study Overview
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Brief Summary
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The purpose of this study is to assess the dose of Hy.D Calcifediol 25 SD/S (a metabolite of vitamin D3) which will achieve the range of mean serum 25(OH)D between 75-100nmol/L in physically frail elderly people after 24 weeks of daily supplementation with different doses of Hy.D Calcifediol 25 SD/S compared to vitamin D3.

Official Title
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Dose Finding Study in Physically Frail Elderly to Measure 25(OH) Vitamin D Levels After Supplementation With Hy.D Calcifediol 25 SD/S and Vitamin D3

Conditions
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Pre-frail Elderly, Frail Elderly

Intervention / Treatment
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* Dietary Supplement: 5 µg/day Hy.D Calcifediol
* Dietary Supplement: 10 µg/day Hy.D Calcifediol
* Dietary Supplement: 15 µg/day Hy.D Calcifediol
* Dietary Supplement: 20 µg/day vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 25(OH)D levels between 25 - 50 nmol/L; Age 65 and older; Physically frail, based on the criteria designed by Fried et al. [1]. Frailty will be defined as a clinical syndrome in which one or more of the following criteria are present: unintentional weight loss (4.5 kg in past year), selfreported exhaustion (CES-D questionnaire), weakness (grip strength), slow walking speed and low physical activity (Minnesota questionnaire). These criteria are easily assessable and have been commonly used to determine frailty; Men and women; Body mass index between 20 and 35 kg/m2 (used for stratification); Willingness and ability to comply with the protocol. Exclusion Criteria: Medical Illness: malabsorption syndrome: known intestinal malabsorption, celiac diseases, inflammatory bowel disease; diseases that may enhance serum calcium concentration: sarcoidosis, lymphoma, kidney stone in the last 10 years, primary hyperparathyroidism; abnormal indices of calcium metabolism, uncontrolled hypocalcaemia; diagnosed renal insufficiency, diagnosed cancer, diagnosed liver failure. Hypercalcemia : serum calcium adjusted for albumin of > 2.6 nmol/L. Medication: bisphosphonate or Parathyroid hormone (PTH) treatment, tuberculostatics, epilepsy medication, interfering with vitamin D metabolism and vitamin D supplementation. Use of vitamin D supplementation in the last three months (excluding multivitamin supplementation). Not willing to stop the use of multivitamin supplementation during the study. (Expected) increase in exposure to sunlight (e.g. travelling to a sunny resort). Patient heavily consumes alcohol containing products defined as greater than (>) 3 drinks (beer, wine, or distilled spirits) of alcoholic beverages per day. Donating blood in the period of 2 months before, until 1 month after the end of the study. Planned surgery. Participation in another clinical trial.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 µg/day Hy.D Calcifediol<br> | Dietary Supplement: 5 µg/day Hy.D Calcifediol<br>* 5 µg/day Hy.D Calcifediol taken together with breakfast for a total period of 24 weeks<br>|
| Experimental: 10 µg/day Hy.D Calcifediol<br> | Dietary Supplement: 10 µg/day Hy.D Calcifediol<br>* 10 µg/day Hy.D Calcifediol taken together with breakfast for a total period of 24 weeks<br>|
| Experimental: 15 µg/day Hy.D Calcifediol<br> | Dietary Supplement: 15 µg/day Hy.D Calcifediol<br>* 15 µg/day Hy.D Calcifediol taken together with breakfast for a total period of 24 weeks<br>|
| Active Comparator: 20 µg/day vitamin D3<br> | Dietary Supplement: 20 µg/day vitamin D3<br>* 20 µg/day vitamin D3 taken together with breakfast for a total period of 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups at baseline | Outcome measurement: Mean serum 25(OH)D levels at baseline before supplementation of three doses of Hy.D and 1 dose of vitamin D3. | Baseline (day 0) | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 4 weeks | Outcome measurement: Mean serum 25(OH)D levels after 4 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 4 weeks after initial compound intake | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 8 weeks | Outcome measurement: Mean serum 25(OH)D levels after 8 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 8 weeks after initial compound intake | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 12 weeks | Outcome measurement: Mean serum 25(OH)D levels after 12 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 12 weeks after initial compound intake | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 16 weeks | Outcome measurement: Mean serum 25(OH)D levels after 16 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 16 weeks after initial compound intake | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 20 weeks | Outcome measurement: Mean serum 25(OH)D levels after 20 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 20 weeks after initial compound intake | 
| Mean serum 25(OH)D levels in Hy.D and vitamin D3 supplemented groups after 24 weeks | Outcome measurement: Mean serum 25(OH)D levels after 24 weeks of supplementation of three doses of Hy.D and 1 dose of vitamin D3. | 24 weeks after initial compound intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive: 25(OH)D3 serum steady state reached? | Assessment if 25(OH)D3 serum levels will reach a steady state after 24 weeks supplementation of 3 doses of Hy.D and 1 dose of vitamin D3 | 0, 4, 8, 12, 16, 20, 24 weeks after study start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D3, Calcifediol 25, Frail, Dose-response