Clinical trial NCT04847947: The Effect of Cholecalciferol in Pre-frail Elderly
Official title: The Effect of Cholecalciferol on Frailty Syndrome in Pre-frail Elderly Receiving Calcium Supplementation : A Study on Handgrip Strength, Gait Speed, Vitamin D Receptor, Insulin Growth Factor-1 and Interleukin-6
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pre-frail Elderly
Keywords: Frailty
Pre-frail
Elderly
Cholecalciferol
Handgrip strength
Gait speed
Vitamin D receptor
Insulin Growth Factor-1
Interleukin-6
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2021-04-19
Enrollment: 120
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Vitamin D plays important role in musculoskeletal health and has been known to influence immune system. Inflammaging is one of risk factors that may contribute to development of frailty in elderly.

The purpose of this study is to determine the effects of cholecalciferol in pre-frail elderly receiving calcium supplementation on handgrip strength, gait speed, vitamin D receptor, IGF-1 and IL-6. Fall incidence and improvement of frailty status will also be assessed.

Detailed description: This is a randomized double-blind placebo-controlled study in pre-frail elderly. Measurement of frailty status based on Fried frailty phenotype criteria (weight loss, weakness, exhaustion, slowness, low physical activity level) .

Subjects who fulfill eligibility criteria will be randomized into 2 groups, one group will received cholecalciferol 4000 IU once daily and the other group will received placebo once daily. Each subjects in both groups will received calcium lactate 500 mg once daily. Intervention will be held for 12 weeks.

Handgrip strength and gait speed will be assessed at baseline, every 4 weeks, and at week 12. Other outcome measures will be assessed at baseline and at week 12.

Eligibility criteria: Inclusion Criteria:

1. Pre-frail elderly
2. Capable to understand and carry-out the instruction

Exclusion Criteria:

1. Allergic to cholecalciferol, calcium, or its components
2. Hypercalcemia (total serum calcium \> 10,5 mg/dL)
3. Unwilling to stop using drug contain vitamin D or vitamin D analog or calcium
4. Using steroid or NSAID routinely
5. Acute illness during inclusion period, eg. pneumonia, stroke attack, acute exacerbation of chronic obstructive pulmonary disease, asthma attack, hypertensive urgency/emergency, acute decompensated heart failure
6. Having condition that can affect measurement of handgrip strength and gait speed, eg. hemiparesis, severe pain in extremities
7. Hepatic cirrhosis, malignancy, autoimmune disease, nephrolithiasis, malabsorption syndrome (eg. chronic diarrhea) , diabetes mellitus with HbA1c \> = 8% in the last 3 months, diabetes mellitus with obvious sign and symptoms of catabolic decompensation (polyphagia, polydipsia, polyuria), chronic kidney disease stage IV-V or decreased renal function with estimated glomerular filtration rate \< 30 ml/minute/1,73 m2
8. Using drug that can affect vitamin D absorption, eg. bile acid sequestrants
9. Cognitive impairment (Abbreviated Mental Test score \< 8)
10. Depression (Geriatric Depression Scale score \> = 10)
11. Unwilling to join the study

Primary outcomes:
measure: Handgrip strength
timeFrame: 12 weeks (evaluation every 4 weeks)
measure: Gait speed
timeFrame: 12 weeks (evaluation every 4 weeks)
Secondary outcomes:
measure: Vitamin D receptor (VDR) monocyte level
timeFrame: 12 weeks
measure: Interleukine 6 (IL-6) monocyte level
timeFrame: 12 weeks
measure: Insulin Growth Factor-1 (IGF-1) monocyte level
timeFrame: 12 weeks
measure: serum VDR level
timeFrame: 12 weeks
measure: Serum IGF-1 level
timeFrame: 12 weeks
measure: serum IL-6 level
timeFrame: 12 weeks
measure: Fall incidence
timeFrame: 12 weeks
measure: Frailty status
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Cipto Mangunkusumo General Hospital
state: DKI Jakarta
Study officials:
affiliation: Division of Geriatric, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo General Hospital
name: Noto Dwimartutie, MD, SpPD-KGer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Setiati S, Anugrahini, Fransiska JE, Tamin TZ, Istanti R. Combination of alfacalcidol and calcium improved handgrip strength and mobility among Indonesian older women: A randomized controlled trial. Geriatr Gerontol Int. 2018 Mar;18(3):434-440. doi: 10.1111/ggi.13201. Epub 2017 Nov 15.
citation: Bray NW, Doherty TJ, Montero-Odasso M. The Effect of High Dose Vitamin D3 on Physical Performance in Frail Older Adults. A Feasibility Study. J Frailty Aging. 2018;7(3):155-161. doi: 10.14283/jfa.2018.18.
citation: Meireles MS, Kamimura MA, Dalboni MA, Giffoni de Carvalho JT, Aoike DT, Cuppari L. Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial. Clin Nutr. 2016 Dec;35(6):1251-1258. doi: 10.1016/j.clnu.2016.04.014. Epub 2016 Apr 26.