Clinical trial NCT01017354: Zurich Disability Prevention Trial
Official title: Monthly Vitamin D to Improve Vitamin D Status and Maintain Function in Pre-frail Older Individuals Living at Home
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Community-dwelling Seniors
History of a Fall in the Previous 12 Months
Keywords: vitamin D
function
falls
25-hydroxyvitamin D
disability
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2009-11-20
Enrollment: 200
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This project was designed to optimizing vitamin D status in prefrail seniors age 70+ living at home and prevent their functional decline. We test 3 arms of monthly vitamin D supplementation. Intermittent dosing will improve adherence and simplify vitamin D supplementation.

Detailed description: We propose a double-blind, randomized controlled trial to test the effectiveness of a

1. Active I (n=70): monthly high-dose vitamin D3 supplement dose (60'000 IU/month, equivalent to 2000 IU daily),
2. Active II (n=70): or a monthly standard vitamin D3 supplement dose combined with 25(OH)D (24'000 IU/month, equivalent to 800 IU daily PLUS 300 mcg 25(OH)D, equivalent to 10 mcg per day)
3. Control (n=70): compared to a standard vitamin D3 supplement dose (24'000 IU/month, equivalent to 800 IU daily)

All individuals will be advised to consume calcium from natural food sources in a daily dose of 600-800 mgs a day, including milk products. Maximal intake of supplemental calcium is restricted to 250 mg per day.

Eligibility criteria: Inclusion criteria:

* Age 70+
* Fall in the last 12 months before screening (with or without a fracture)
* Living at home (community-dwelling)
* Men or women
* Mobile with or without walking aid - have to be able to use public transportation to attend the clinical visits at the trial centre
* Score of at least 27 at the screening Folstein Mini Mental test + normal clock test
* Patient understands the study procedures, alternative treatments available and risks involved with the study, and voluntarily agrees to participate by giving a written informed consents.
* Patient meets the entry minimal requirements based on routine clinical laboratory safety screening tests and the Folstein mini mental status (score 27+ required) performed at the Screening Visit.
* Patient is willing to perform all study tests, attend all required office visits, and provide blood and urine samples.

Exclusion criteria:

* Serum calcium adjusted for albumin of \> 2.6 nmol/l
* Pathologic fracture in the last year (except for fractures due to osteoporosis)
* Chemo therapy / Radiation due to cancer in the last year
* Treatment which has an effect on bone metabolism (e.g. bisphosphonate, PTH, calcitonin, chronic cortisone intake \> XYmg/day for more than XY month/years (except for inhalation and sporadic infiltration))
* Oral vitamin D intake of more than 800 IU per day
* Unwilling to stop calcium supplementation and vitamin D supplementation during the trial (maximal calcium supplement intake 250mg/d; no additional vitamin D supplementation)
* Severe visual or hearing impairment
* Unwilling or unable to take study medication
* Diseases with a risk of recurrent falling (e.g. Parkinson's disease/syndrome, Hemiplegia after stroke, symptomatic stenosis of the spinal canal, polyneuropathy, epilepsy, recurring vertigo, recurring syncope)
* BMI \>= 40
* Estimated creatinine clearance \< 15 ml/min (estimated Creatinine Clearance Cockcroft and Gault)
* Malabsorption syndrome (celiac diseases, inflammatory bowl disease)
* Diseases that may enhance serum calcium: sarcoidosis, lymphoma, primary hyperparathyroidism
* kidney stone in the last 10 years
* Abnormal indices of calcium metabolism, uncontrolled hypocalcemia.
* Patient heavily consumes alcohol containing products defined as greater than (\>) 3 drinks (beer, wine, or distilled spirits) of alcoholic beverages per day.
* Patient is unlikely to adhere to the study procedures, to keep appointments, or is planning to relocate during the study.
* Patients who are planning a stay in a "sunny" location (e.g. winter sun resort) for more than two months per year
* Medication which has an effect on 25-hydroxyvitamin D level (e.g. certain anticonvulsants (e.g. Phenobarbital, Carbamazepin, Phenytoin))
* M. Paget (Ostitis deformans)
* inflammatory arthritis (e.g. rheumatoid arthritis, reiter syndrome, psoriasis arthritis)

Primary outcomes:
measure: functional decline (proportion of individuals with functional decline based on binary repeated measure assessment across 4 lower extremity tests)
timeFrame: 6 and 12 months
measure: Improving 25-hydroxyvitamin D levels in late winter and late summer - Percent of individuals reaching desirable 25-hydroxyvitamin D levels of at least 75 nmol/l in late winter and in late summer
timeFrame: 6 and 12 months
Secondary outcomes:
measure: Safety at baseline, 2 weeks, 6 months, 12 months • Serum calcium adjusted for albumin • Serum creatinine • Urinary calcium/creatinine ratio
timeFrame: 2 weeks, 6 months, 12 months
measure: Balance/Gait while walking combined with a cognitive task
timeFrame: 12 months
measure: Short Physical Performance Test Battery
timeFrame: 6 months, 12 months
measure: Timed 4 m walk
timeFrame: 6 months, 12 months
measure: Musculoskeletal pain assessed with the McGill pain map
timeFrame: 6 months and 12 months
measure: systolic and diastolic blood pressure, heart rate
timeFrame: 6 month and 12 months
measure: Rate of falls, all, injurious falls (diary, monthly phone calls, and hotline)
timeFrame: 12 months
measure: grip strength
timeFrame: 6 months and 12 months
measure: Bone density at the spine and hip, whole body
timeFrame: 6 months and 12 months
measure: incident vertebral fractures (iDXA morphometry)
timeFrame: 12 months
measure: muscle mass, incident sarcopenia
timeFrame: 6 and 12 months
measure: Health care utilization: in collaboration with insurance companies for outpatient and inpatient health care costs.
timeFrame: 12 months
measure: Quality of life (SF 12 / EuroQuol)
timeFrame: 6 months and 12 months
measure: Rate of hospital admission (fall-related injury, infections, other)
timeFrame: 12 months
measure: Serum N-telopeptides and other markers of bone remodeling
timeFrame: 6 months and 12 months
measure: Upper and lower respiratory tract infections, any infections, infections that lead to inpatient care
timeFrame: 12 months
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Centre on Aging and Mobility
state: ZH
Study officials:
affiliation: University Hospital Zurich, Centre on Aging and Mobility
name: Heike Bischoff Ferrari, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, Dick W, Willett WC, Egli A. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. JAMA Intern Med. 2016 Feb;176(2):175-83. doi: 10.1001/jamainternmed.2015.7148.