The Effect of Calcifediol (Hy.D 25 SD/S) and Vitamin D3 on Muscle Strength in a Frail Elderly Population (D-Fit)

The Effect of Calcifediol (Hy.D 25 SD/S) and Vitamin D3 on Muscle Strength in a Frail Elderly Population: a Randomized, Double-blind, Placebo-controlled Trial.

In an ageing population, the need for interventions to help older people remain healthy, active and independent for as long as possible, increases. Although several studies suggest a beneficial effect of vitamin D3 on maintaining or improving muscle strength and physical functioning, particularly in vulnerable populations, results are contradicting. Randomized, placebo-controlled trials are needed to further establish the effect of vitamin D on muscle strength in the frail elderly population.The primary aim of this study is to determine the effect of daily supplementation with two different forms of vitamin D on muscle strength in frail elderly people over a period of 24 weeks.

Study Overview

• Status: Completed
• Conditions: Elderly, Frail; Deficiency, Vitamin D
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Calcifediol 10ug/day; Dietary supplement: Vitamin D3 20ug/day

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6703HD
      • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 25(OH)D levels 20-50 nmol/L.
• age 65 or older.
• physically frail (pre-frail or frail, based on the criteria designed by Fried et al.) (30). 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), self-reported exhaustion (CES-D questionnaire), weakness (grip strength), slow walking speed and low physical activity (Minnesota questionnaire). More details on these criteria are described in chapter 6.3.2.
• body mass index between 18.5 and 35 kg/m2.
• willingness and ability to comply with the protocol, including performance of the knee extension strength test.

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; currently diagnosed or undergoing treatment.
• Hypercalcemia: serum calcium adjusted for albumin of > 2.6 nmol/L.
• Medication: interfering with vitamin D metabolism and vitamin D supplementation (bisphosphonate, PTH treatment, tuberculostatica, anti-epileptica).
• Subject not able (when medically necessary/ advised) or not willing to stop the use of vitamin D containing supplements during the study.
• (Expected) increase in exposure to sunlight (e.g. travelling to a sunny resort) during intervention period.
• Patient heavily consumes alcohol containing products defined as greater than > 21 drinks of alcoholic beverages per week.
• Planned surgery which can affect study measures (taking into account duration of hospitalisation and recovery).
• Participation in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcifediol 10 ug/day; Capsule with 10 ug/day Calcifediol taken together with breakfast for a total period of 24 weeks.	Dietary supplement: Calcifediol 10ug/day; Other Names: Hy.D
Experimental: Vitamin D3 20 ug/day; Capsule with 20 ug/day Vitamin D3 taken together with breakfast for a total period of 24 weeks.	Dietary supplement: Vitamin D3 20ug/day; Other Names: Cholecalciferol
Placebo Comparator: Placebo; Capsule without active ingredients, taken together with breakfast for a total period of 24 weeks.	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle strength, knee extension strength (measured by Biodex System)	measured by Biodex System	baseline, week 12, end of study (after 24 weeks supplementation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in knee flexion strength (measured by Biodex System)	measured by Biodex System	baseline, week 12, end of study (after 24 weeks supplementation)
Change in handgrip strength		baseline, week 12, end of study (after 24 weeks supplementation)
Change in SPPB		baseline, week 12, end of study (after 24 weeks supplementation)
Change in Timed Up and Go test		baseline, week 12, end of study (after 24 weeks supplementation)
Change in Postural Body Sway		baseline, week 12, end of study (after 24 weeks supplementation)
Change in serum Vitamin D3		baseline, week 12, end of study (after 24 weeks supplementation)
Change in serum 25(OH)D		baseline, week 12, end of study (after 24 weeks supplementation)
Change in serum 1,25(OH)2D3		baseline, week 12, end of study (after 24 weeks supplementation)
Change in serum 24,25(OH)2D		baseline, week 12, end of study (after 24 weeks supplementation)
Frequency of falling		baseline, week 12, end of study (after 24 weeks supplementation)
Change in muscle fibre type and size (Biopsy)	Biopsy	baseline, end of study (after 24 weeks supplementation)
Change in body composition (DEXA-scan)	DEXA-scan	baseline, end of study (after 24 weeks supplementation)
Change in cognitive functioning (Trail making, Stroop-test, Letter fluency)	Trail making, Stroop-test, Letter fluency	baseline, end of study (after 24 weeks supplementation)
Change in vital Signs (blood pressure and heart rate)	blood pressure and heart rate	baseline, week 12, end of study (after 24 weeks supplementation)
Change in neuromuscular measurements (MUNIX, MUSIX by EMG)	MUNIX, MUSIX by EMG	baseline, end of study (after 24 weeks supplementation)

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: DSM Nutritional Products, Inc.; Top Institute Food and Nutrition

Publications and helpful links

General Publications

• Hangelbroek RWJ, Vaes AMM, Boekschoten MV, Verdijk LB, Hooiveld GJEJ, van Loon LJC, de Groot LCPGM, Kersten S. No effect of 25-hydroxyvitamin D supplementation on the skeletal muscle transcriptome in vitamin D deficient frail older adults. BMC Geriatr. 2019 May 28;19(1):151. doi: 10.1186/s12877-019-1156-5.
• Vaes AMM, Tieland M, Toussaint N, Nilwik R, Verdijk LB, van Loon LJC, de Groot LCPGM. Cholecalciferol or 25-Hydroxycholecalciferol Supplementation Does Not Affect Muscle Strength and Physical Performance in Prefrail and Frail Older Adults. J Nutr. 2018 May 1;148(5):712-720. doi: 10.1093/jn/nxy024.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Estimate): January 11, 2016
• Last Update Submitted That Met QC Criteria: January 8, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: muscle strength; physical performance; vitamin D3; Cholecalciferol; Calcifediol
• Additional Relevant MeSH Terms: Nutrition Disorders; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcifediol
• Other Study ID Numbers: NL48127.081.148