Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (Acronym: DO-HEALTH)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- University of Zurich
- Enrollment
- 2,157
- Locations
- 7
- Primary Endpoint
- Cardio-vascular: Systolic and diastolic blood pressure change
Study Overview
Brief Summary
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/
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
VitD-Placebo-FlexiblityExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
Intervention: Flexibility Home Exercise (Procedure)
VitD-Omega3-FlexibilityExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
Intervention: Omega 3 fatty acids (Drug)
VitD-Omega3-StrengthExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
Intervention: Vitamin D3 (Drug)
VitD-Omega3-StrengthExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
Intervention: Omega 3 fatty acids (Drug)
VitD-Omega3-StrengthExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
Intervention: Strength Home Exercise (Procedure)
VitD-Omega3-FlexibilityExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
Intervention: Vitamin D3 (Drug)
VitD-Omega3-FlexibilityExercise
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
Intervention: Flexibility Home Exercise (Procedure)
Placebo-Omega3-StrengthExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
Intervention: Omega 3 fatty acids (Drug)
Placebo-Omega3-StrengthExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
Intervention: Strength Home Exercise (Procedure)
Placebo-Omega3-FlexibilityExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
Intervention: Omega 3 fatty acids (Drug)
Placebo-Omega3-FlexibilityExercise
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
Intervention: Flexibility Home Exercise (Procedure)
VitD-Placebo-StrengthExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
Intervention: Vitamin D3 (Drug)
VitD-Placebo-StrengthExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
Intervention: Strength Home Exercise (Procedure)
VitD-Placebo-FlexiblityExercise
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
Intervention: Vitamin D3 (Drug)
Placebo-Placebo-StrengthExercise
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
Intervention: Strength Home Exercise (Procedure)
Placebo-Placebo-FlexibilityExercise
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
Intervention: Flexibility Home Exercise (Procedure)
Outcomes
Primary Outcomes
Cardio-vascular: Systolic and diastolic blood pressure change
Time Frame: Baseline, 12, 24 and 36 months
Standardized blood pressure assessment in sitting position
Brain: Cognitive decline
Time Frame: Baseline, 12, 24 and 36 months
Montreal Cognitive Assessment (MoCA)
Bone: Incident non-vertebral fractures over 36 months
Time Frame: over 36 months
Confirmed by medical and/or x-ray reports
Muscle: Functional decline (lower extremity function)
Time Frame: Baseline, 12, 24 and 36 months
Measured with the SPPB (short physical performance test battery)
Immunity: Rate of any infections
Time Frame: Baseline, and every 3 months up to 36 months
3-monthly incident infection protocol
Secondary Outcomes
- Bone: Incident total fractures(36 months)
- Bone: Incident hip fractures(36 months)
- Muscle: reaction time and grip strength(Baseline, 12,24,36 months)
- Muscle: Muscle mass decrease at upper and lower extremities(Baseline, 12,24,36 months)
- Muscle/Bone: musculoskeletal pain(Baseline, 12,24, and 36 months)
- Bone: Incident vertebral fractures(36 months)
- Muscle: Dual tasking 10-meter gait speed(Baseline, 12,24 and 36 months)
- Bone: Bone mineral density decrease at the lumbar spine and hip(Baseline, 12, 24, and 36 months)
- Muscle: Rate of falls(Assessed every 3 months over 36 months)
- Brain: mental health decline(Baseline, 12,24, and 36 months)
- Brain/Muscle: Dual tasking gait variability(Baseline, 12, 24 and 36 months)
- Immunity: Incident severe infections that lead to hospital admission(36 months)
- Brain: Incident Depression(36 months)
- Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritis(Baseline, 12, 24 and 36 months)
- Cardio-vascular: Incident Hypertension(36 months)
- Immunity: Rate of upper respiratory infections / rate of flu-like illness(36 months)
- Cartilage/Bone: Rate of knee buckling(Baseline, 12,24,36 months)
- Cartilage/Bone: NSAID use / number of joints with pain(Baseline, 12, 24, 36 months)
- Global Health: Quality of life(Every 6 months)
- Global Health: Incident nursing home admission(36 months)
- Global Health: Mortality(36 months)
- Gastro-Intestinal: rate of GI symptoms(Baseline, 12, 24 and 36 months)
- Dental: Decline in oral health(Baseline, 12,24 and 36 months)
- Dental: Tooth loss(36 months)
- Glucose-Metabolic: Body composition(Baseline, 12, 24, 36 months)
- Kidney: Decline in kidney function(Baseline, 12, 24, and 36 months)
- Glucose-Metabolic: Change in fasting glucose, insulin levels (QUICKI, HOMA index)(Baseline, 12,24,36 months)
- Global Health: Incident disability regarding activities of daily living(Baseline, 12, 24 and 36 months)
Investigators
Heike Bischoff-Ferrari
Director, Centre on Aging and Mobility
University of Zurich