DO-HEALTH / Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial

The 3 primary treatment comparisons are:

• 2000 IU vitamin D per day compared to placebo (controlling for the other treatment strategies)
• 1 g of omega-3 fatty acids (EPA+DHA, ratio 1:2, from marine algae) compared to placebo (controlling for the other treatment strategies)
• Home exercise program (muscle strength) of 30 minutes 3 times a week compared to a control exercise program (joint flexibility) 30 minutes 3 times a week

Follow-up: DO-HEALTH seniors will be followed for 3 years, in-person, and in 3-monthly intervals (4 clinical visits and 9 phone calls) at the 7 recruitment centers.

Study population: DO-HEALTH will enroll seniors age 70 years and older. To represent the largest part of the senior population, DO-HEALTH will recruit community-dwelling seniors. However, to represent also the pre-frail population at risk of institutionalization, at least 40% of seniors will be enrolled based on a fall with or without a fracture in the year before DO-HEALTH enrolment.

Study Design: This is a randomized, double-blind, placebo-controlled, 2×2×2 factorial design clinical trial.

Recruitment Centers: The trial will be performed at 7 recruitment centers located in 5 countries: Switzerland (University of Zurich, Basel University Hospital, Geneva University Hospital), France (University of Toulouse Hospital Centre), Germany (Charité Berlin), Portugal (University of Coimbra), and Austria (Innsbruck Medical University).

Randomization: Stratified block randomization. Labeling of study intervention will be performed by a central randomization centre in Switzerland.

Stratification variables: recruitment centre (7 centers), fall during previous 12 months (yes/no), gender, and age (70 - 84 and 85+). At least 40% of Seniors among those who fell or did not fall during the last year will be enforced at each of the 7 recruitment centers. Gender and age distribution will be monitored within each recruitment centre with the DO-HEALTH randomization software. If gross imbalance (less than 30% of fallers/non-fallers in a stratum) is detected within a centre, recruitment strategies for the centre will be adapted to boost recruitment of participants of underrepresented category.

website DO-HEALTH: http://do-health.eu/wordpress/

Inclusion criteria

• Age 70 years or older
• Mini Mental State Examination Score of at least 24
• Living in the community
• Sufficiently mobile to come to the study centre
• Able to walk 10 meters with or without a walking aid and able to get in and out of a chair without help
• Able to swallow study capsules
• Able and willing to participate, sign informed consent (including consent to analyze all samples until drop-out or withdrawal) and cooperate with study procedures

Exclusion criteria

• Consumption of more than 1000 IU vitamin D/day in the 36 months prior to enrollment, or a bolus of 300'000 IU or more in the last 12 month prior to enrollment, and/ or unwillingness to limit vitamin D intake to the current standard of 800 IU/day of vitamin D during the course of the trial. Provision 1: an individual who consumed an average vitamin D dose between 1000 and 2000 IU vitamin D/day in the 3 months prior to enrollment, may be enrolled after a 3-month wash-out period where the maximum daily intake is limited to 800 IU vitamin D. Provision 2: an individual who consumed an average vitamin D dose higher than 2000 IU/day in the 3 months prior to enrollment, may be enrolled after a 6-month wash-out period where the maximum daily intake is limited to 800 IU vitamin D.
• Unwillingness to limit calcium supplement dose to 500 mg per day for the duration of the trial
• Taking omega-3 fat supplements in the 3 month prior to enrolment and unwilling to forgo their use for the duration of the trial
• Use of any active vitamin D metabolite (i.e. Rocaltrol, alphacalcidiol), PTH treatment (i.e. Teriparatide), or Calcitonin at baseline and unwillingness to forego these treatments during the course of the trial
• Current or recent (previous 4 months) participation in another clinical trial, or plans of such participation in the next 3 years (corresponding to DO-HEALTH length)
• Presence of the following diagnosed health conditions in the last 5 years: history of cancer (except non-melanoma skin cancer); myocardial infarction, stroke, transient ischemic attack, angina pectoris, or coronary artery intervention
• Severe renal impairment (creatinine clearance = 15 ml/min) or dialysis, hypercalcaemia (> 2.6 mmol/l)
• Hemiplegia or other severe gait impairment
• History of hypo- or primary hyperparathyroidism
• Severe liver disease
• History of granulomatous diseases (i.e. tuberculosis, sarcoidosis)
• Major visual or hearing impairment or other serious illness that would preclude participation
• Living with a partner who is enrolled in DO-HEALTH (i.e. only one person per household can be enrolled)
• Living in assisted living situations or a nursing home
• Temporary exclusion: acute fracture in the last 6 weeks
• Epilepsy and/or use of anti-epileptic drugs
• Individuals who fell more than 3 times in the last month
• Osteodystrophia deformans (M. Paget, Paget's disease)
• For study centers in Germany only: persons who are institutionalized / in prison by court order (§40, Abs. 1, Art. 4, "Gesetz über den Verkehr mit Arzneimitteln").