- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01745263
DO-HEALTH / Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (DO-HEALTH)
Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (Acronym: DO-HEALTH)
The European population is aging rapidly which poses a challenge on the individual, the European societies, and health care systems. Among the most promising public health interventions that may extend healthy life expectancy at older age are vitamin D, marine omega-3 fatty acids and physical exercise. However, their individual and combined effects have yet to be confirmed in a clinical trial.
The broad aim of DO-HEALTH is to prolong healthy life expectancy in European seniors. The specific aim is to establish whether vitamin D, omega-3 fatty acids, and a simple home exercise program will prevent disease at older age.
To achieve these aims, DO-HEALTH will enroll 2152 community-dwelling men and women who are 70 years and older, an age when chronic diseases increase substantially. The DO-HEALTH seniors will be recruited from 7 European cities (Zurich, Basel, Geneva, Toulouse, Berlin, Innsbruck and Coimbra) and will be randomized in a 2x2x2 factorial design trial to a simple home exercise program and/or vitamin D, and/or omega-3 fatty acids, over a 3 year period. This will allow to test the individual and the combined benefit of the interventions in the prevention of 5 primary endpoints: incident non-vertebral fractures; functional decline; systolic and diastolic blood pressure change; cognitive decline; and the rate of any infection. Key secondary endpoints include incidence of hip fractures, rate of falls, severity of pain in symptomatic knee osteoarthritis, gastro-intestinal symptoms, mental and oral health, quality of life, and mortality.
All clinical endpoints will be supported by a large DO-HEALTH biomarker study to evaluate the effect of the interventions at the cellular level of multi-organ function. DO-HEALTH will further evaluate reasons why or why not seniors adhere to the 3 interventions, and will assess their cost-benefit in a health economic model based on documented health care utilization and observed incidence of chronic disease.
website DO-HEALTH: http://do-health.eu/wordpress/
Study Overview
Status
Intervention / Treatment
Detailed Description
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/
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Innsbruck, Austria
- University of Innsbruck
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Toulouse, France
- University of Toulouse - Centre de Recherche - Gérontopôle Hôpital La Grave
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Berlin, Germany
- Charite Berlin
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Coimbra, Portugal
- University of Coimbra - Clínica Universitária de Reumatologia
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Basel, Switzerland
- Basel University
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Geneva, Switzerland
- Hôpitaux universitaires de Genève
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ZH
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Zurich, ZH, Switzerland, 8091
- Centre on Aging and Mobility, University of Zurich and City Hospital Waid
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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").
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: VitD-Omega3-StrengthExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
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2000 IU/d
Other Names:
Ratio EPA:DHA = 1:2 1 g/d
Other Names:
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Active Comparator: VitD-Omega3-FlexibilityExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
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2000 IU/d
Other Names:
Ratio EPA:DHA = 1:2 1 g/d
Other Names:
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Active Comparator: Placebo-Omega3-StrengthExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
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Ratio EPA:DHA = 1:2 1 g/d
Other Names:
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Active Comparator: Placebo-Omega3-FlexibilityExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
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Ratio EPA:DHA = 1:2 1 g/d
Other Names:
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Active Comparator: VitD-Placebo-StrengthExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
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2000 IU/d
Other Names:
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Active Comparator: VitD-Placebo-FlexiblityExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
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2000 IU/d
Other Names:
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Active Comparator: Placebo-Placebo-StrengthExercise
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
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Sham Comparator: Placebo-Placebo-FlexibilityExercise
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Bone: Incident non-vertebral fractures over 36 months
Time Frame: over 36 months
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Confirmed by medical and/or x-ray reports
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over 36 months
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Muscle: Functional decline (lower extremity function)
Time Frame: Baseline, 12, 24 and 36 months
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Measured with the SPPB (short physical performance test battery)
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Baseline, 12, 24 and 36 months
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Cardio-vascular: Systolic and diastolic blood pressure change
Time Frame: Baseline, 12, 24 and 36 months
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Standardized blood pressure assessment in sitting position
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Baseline, 12, 24 and 36 months
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Brain: Cognitive decline
Time Frame: Baseline, 12, 24 and 36 months
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Montreal Cognitive Assessment (MoCA)
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Baseline, 12, 24 and 36 months
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Immunity: Rate of any infections
Time Frame: Baseline, and every 3 months up to 36 months
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3-monthly incident infection protocol
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Baseline, and every 3 months up to 36 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bone: Incident hip fractures
Time Frame: 36 months
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Based on medical records and/or x-ray reports
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36 months
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Bone: Incident total fractures
Time Frame: 36 months
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Combined non-vertebral and vertebral fractures among subgroup of 1502 participants with DXA vertebral morphometry assessment
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36 months
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Bone: Incident vertebral fractures
Time Frame: 36 months
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Based on DXA vertebral morphometry among subset of 1502 participants
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36 months
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Bone: Bone mineral density decrease at the lumbar spine and hip
Time Frame: Baseline, 12, 24, and 36 months
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Assessed in a subset of 1502 participants with DXA measurements
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Baseline, 12, 24, and 36 months
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Muscle: Rate of falls
Time Frame: Assessed every 3 months over 36 months
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Any low trauma fall, injurious fall
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Assessed every 3 months over 36 months
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Muscle: reaction time and grip strength
Time Frame: Baseline, 12,24,36 months
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Reaction time will be assessed with the repeated sit-to-stand test; grip strength will be assessed with the Martin Vigorimeter
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Baseline, 12,24,36 months
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Muscle: Muscle mass decrease at upper and lower extremities
Time Frame: Baseline, 12,24,36 months
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Subset of 1502 participants with DXA measurements
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Baseline, 12,24,36 months
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Muscle: Dual tasking 10-meter gait speed
Time Frame: Baseline, 12,24 and 36 months
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Baseline, 12,24 and 36 months
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Muscle/Bone: musculoskeletal pain
Time Frame: Baseline, 12,24, and 36 months
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Assessed with the McGill questionnaire
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Baseline, 12,24, and 36 months
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Cardio-vascular: Incident Hypertension
Time Frame: 36 months
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36 months
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Brain: mental health decline
Time Frame: Baseline, 12,24, and 36 months
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Assessed with Geriatric Depression Scale
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Baseline, 12,24, and 36 months
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Brain: Incident Depression
Time Frame: 36 months
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36 months
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Brain/Muscle: Dual tasking gait variability
Time Frame: Baseline, 12, 24 and 36 months
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Subset of 250 participants
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Baseline, 12, 24 and 36 months
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Immunity: Rate of upper respiratory infections / rate of flu-like illness
Time Frame: 36 months
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Assessed with infection protocol every 3 months
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36 months
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Immunity: Incident severe infections that lead to hospital admission
Time Frame: 36 months
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36 months
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Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritis
Time Frame: Baseline, 12, 24 and 36 months
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Assessed with the KOOS questionnaire.
Knee OA assessment with modified ACR criteria.
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Baseline, 12, 24 and 36 months
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Cartilage/Bone: Rate of knee buckling
Time Frame: Baseline, 12,24,36 months
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Questionnaire-based.
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Baseline, 12,24,36 months
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Cartilage/Bone: NSAID use / number of joints with pain
Time Frame: Baseline, 12, 24, 36 months
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Assessed by questionnaire and homunculus figure
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Baseline, 12, 24, 36 months
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Dental: Decline in oral health
Time Frame: Baseline, 12,24 and 36 months
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Assessed with questionnaire.
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Baseline, 12,24 and 36 months
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Dental: Tooth loss
Time Frame: 36 months
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Assessed by tooth count at every clinical visit
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36 months
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Gastro-Intestinal: rate of GI symptoms
Time Frame: Baseline, 12, 24 and 36 months
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Assessed with ROME III questionnaire.
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Baseline, 12, 24 and 36 months
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Glucose-Metabolic: Change in fasting glucose, insulin levels (QUICKI, HOMA index)
Time Frame: Baseline, 12,24,36 months
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Laboratory measures at the Central DO-HEALTH Laboratory (Institute of Clinical Chemistry at the University Hospital Zurich)
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Baseline, 12,24,36 months
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Glucose-Metabolic: Body composition
Time Frame: Baseline, 12, 24, 36 months
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Subset of 1502 participants with DXA measurements
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Baseline, 12, 24, 36 months
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Kidney: Decline in kidney function
Time Frame: Baseline, 12, 24, and 36 months
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Blood creatinine levels and estimated glomerular filtration rate
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Baseline, 12, 24, and 36 months
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Global Health: Quality of life
Time Frame: Every 6 months
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Assessed with questionnaire (EuroQuol).
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Every 6 months
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Global Health: Incident disability regarding activities of daily living
Time Frame: Baseline, 12, 24 and 36 months
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Assessed with HAQ-PROMIS questionnaire
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Baseline, 12, 24 and 36 months
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Global Health: Incident nursing home admission
Time Frame: 36 months
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36 months
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Global Health: Mortality
Time Frame: 36 months
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36 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biomarker endpoints
Time Frame: Baseline, 12, 24, and 36 months
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Baseline, 12, 24, and 36 months
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Bone: Incident repeat fractures
Time Frame: 36 months
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Any repeat non-vertebral fractures in all participants, vertebral fractures and total fractures among subset of 1502 seniors with yearly DXA measurements
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36 months
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BONE: Functional recovery after long bone fracture
Time Frame: 36 months
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36 months
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Muscle: Incident sarcopenia / incident frailty / decline in physical function
Time Frame: 36 months
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Incident sarcopenia (among subset of 1502 seniors with yearly DXA measurements), incident frailty (questionnaire), decline in physical activity (questionnaire)
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36 months
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Cardio-vascular: Major cardio-vascular events
Time Frame: 36 months
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Major cardiovascular events as a composite endpoint (any event: myocardial infarction, stroke, revascularization procedures of CABG and PCI, incident congestive heart disease, cardiovascular mortality); individual endpoints: myocardial infarction, stroke, incident congestive heart disease, and cardiovascular mortality (assessed every 3 months over 36 months)
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36 months
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Brain: incident dementia
Time Frame: 36 months
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36 months
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Immunity: Incident cancer / rate of implant infections / rate of gastro-intestinal infections
Time Frame: 36 months
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Incident cancer (any cancer, gastro-intestinal, breast cancer in women, prostate cancer in men); rate of implant infections after total hip or knee replacement (due to fracture or osteoarthritis); rate of gastro-intestinal infections
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36 months
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Cartilage/bone: Incident osteoarthritis
Time Frame: Baseline, 12, 24, and 36 months
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Incident symptomatic knee osteoarthritis; incident symptomatic hip osteoarthritis, incident symptomatic hand osteoarthritis; composite endpoint: incident symptomatic knee, hip or hand osteoarthritis; severity of hip pain in those with prevalent symptomatic hip osteoarthritis, severity of hand pain in those with prevalent symptomatic hand osteoarthritis
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Baseline, 12, 24, and 36 months
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Adherence laboratory
Time Frame: Baseline, 12, 24, and 36 months
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Serum 25(OH)D concentrations (measured both by an automated assay and HPLCMS/MS) and plasma PUFA concentrations (EPA, AA, DPA, DHA; measured by a sensitive and selective assay based on gas chromatography coupled to mass spectrometry detection (GC-MS)) in all participants
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Baseline, 12, 24, and 36 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Heike Bischoff Ferrari, Prof MD, "Centre on Aging and Mobility" University of Zurich, University Hospital Zurich and City Hospital Waid.
Publications and helpful links
General Publications
- Bischoff-Ferrari HA, Willett WC, Manson JE, Dawson-Hughes B, Manz MG, Theiler R, Braendle K, Vellas B, Rizzoli R, Kressig RW, Staehelin HB, Da Silva JAP, Armbrecht G, Egli A, Kanis JA, Orav EJ, Gaengler S. Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial. Front Aging. 2022 Apr 25;3:852643. doi: 10.3389/fragi.2022.852643. eCollection 2022.
- de Godoi Rezende Costa Molino C, Chocano-Bedoya PO, Sadlon A, Theiler R, Orav JE, Vellas B, Rizzoli R, Kressig RW, Kanis JA, Guyonnet S, Lang W, Egli A, Bischoff-Ferrari HA; DO-HEALTH Research Group. Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH. BMJ Open. 2022 Apr 29;12(4):e051881. doi: 10.1136/bmjopen-2021-051881.
- Schietzel S, Chocano-Bedoya PO, Sadlon A, Gagesch M, Willett WC, Orav EJ, Kressig RW, Vellas B, Rizzoli R, da Silva JAP, Blauth M, Kanis JA, Egli A, Bischoff-Ferrari HA. Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries. BMC Geriatr. 2022 Mar 2;22(1):174. doi: 10.1186/s12877-022-02755-8.
- Bischoff-Ferrari HA, Vellas B, Rizzoli R, Kressig RW, da Silva JAP, Blauth M, Felson DT, McCloskey EV, Watzl B, Hofbauer LC, Felsenberg D, Willett WC, Dawson-Hughes B, Manson JE, Siebert U, Theiler R, Staehelin HB, de Godoi Rezende Costa Molino C, Chocano-Bedoya PO, Abderhalden LA, Egli A, Kanis JA, Orav EJ; DO-HEALTH Research Group. Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial. JAMA. 2020 Nov 10;324(18):1855-1868. doi: 10.1001/jama.2020.16909.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KEK-ZH-2012-0249
- DO-HEALTH (Other Grant/Funding Number: European Commission (project number 278588))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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