Zurich Disability Prevention Trial (ZDPT)

• functional decline (proportion of individuals with functional decline based on binary repeated measure assessment across 4 lower extremity tests) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
• 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 [ Time Frame: 6 and 12 months ] [ Designated as safety issue: Yes ]

• Safety at baseline, 2 weeks, 6 months, 12 months • Serum calcium adjusted for albumin • Serum creatinine • Urinary calcium/creatinine ratio [ Time Frame: 2 weeks, 6 months, 12 months ] [ Designated as safety issue: Yes ]
• Balance/Gait while walking combined with a cognitive task [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Short Physical Performance Test Battery [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
• Timed 4 m walk [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
• Musculoskeletal pain assessed with the McGill pain map [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
• systolic and diastolic blood pressure, heart rate [ Time Frame: 6 month and 12 months ] [ Designated as safety issue: No ]
• Rate of falls, all, injurious falls (diary, monthly phone calls, and hotline) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• grip strength [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
• Bone density at the spine and hip, whole body [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
• incident vertebral fractures (iDXA morphometry) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• muscle mass, incident sarcopenia [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
• Health care utilization: in collaboration with insurance companies for outpatient and inpatient health care costs. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Quality of life (SF 12 / EuroQuol) [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
• Rate of hospital admission (fall-related injury, infections, other) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Serum N-telopeptides and other markers of bone remodeling [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
• Upper and lower respiratory tract infections, any infections, infections that lead to inpatient care [ Time Frame: 12 months ] [ Designated as safety issue: No ]

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.

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.

• Community-dwelling Seniors
• History of a Fall in the Previous 12 Months

• Drug: Hidroferol® (ES)
  24000 IU vitamin D3 orally and once per month plus 300 mcg 25(OH)D orally and once per month
• Dietary Supplement: ViDe3 (CH)
  60000 vitamin D3 orally and once per month
• Dietary Supplement: ViDe3 (CH)
  24000 Vitamin D3 orally and once per month

• Experimental: High-dose vitamin D3
  monthly high-dose vitamin D3 supplement dose (60'000 IU/month, equivalent to 2000 IU daily)
  Intervention: Dietary Supplement: ViDe3 (CH)
• Experimental: standard vitamin D + 25(OH)D
  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)
  Intervention: Drug: Hidroferol® (ES)
• Active Comparator: standard vitamin D
  standard vitamin D3 supplement dose (24'000 IU/month, equivalent to 800 IU daily)
  Intervention: Dietary Supplement: ViDe3 (CH)

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 25 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 25+ 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)