Overview

This trial is active, not recruiting.

Condition improve healthy ageing in seniors; prevent disease at older age
Treatments vitamin d3, omega 3 fatty acids, strength home exercise, flexibility home exercise
Phase phase 3
Sponsor University of Zurich
Collaborator Recruitment Partners
Start date December 2012
End date November 2017
Trial size 2159 participants
Trial identifier NCT01745263, DO-HEALTH, KEK-ZH-2012-0249

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: the risk of incident non-vertebral fractures; the risk of functional decline; the risk of blood pressure increase; the risk of cognitive decline; and the rate of any infection. Key secondary endpoints include risk of hip fracture, rate of falls, pain in symptomatic knee osteoarthritis, gastro-intestinal symptoms, mental and oral health, quality of life, and life-expectancy.

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/ website EC: http://ec.europa.eu/research/health/medical-research/human-development-and-ageing/projects/do-health_en.html

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model factorial assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Active Comparator)
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
vitamin d3 Cholecalciferol
2000 IU/d
omega 3 fatty acids Eicosapentaenoic acid AND Docosahexaenoic acid
Ratio EPA:DHA = 1:2 1 g/d
strength home exercise
(Active Comparator)
Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
vitamin d3 Cholecalciferol
2000 IU/d
omega 3 fatty acids Eicosapentaenoic acid AND Docosahexaenoic acid
Ratio EPA:DHA = 1:2 1 g/d
flexibility home exercise
(Active Comparator)
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week)
omega 3 fatty acids Eicosapentaenoic acid AND Docosahexaenoic acid
Ratio EPA:DHA = 1:2 1 g/d
strength home exercise
(Active Comparator)
Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week)
omega 3 fatty acids Eicosapentaenoic acid AND Docosahexaenoic acid
Ratio EPA:DHA = 1:2 1 g/d
flexibility home exercise
(Active Comparator)
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
vitamin d3 Cholecalciferol
2000 IU/d
strength home exercise
(Active Comparator)
Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
vitamin d3 Cholecalciferol
2000 IU/d
flexibility home exercise
(Active Comparator)
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week)
strength home exercise
(Sham Comparator)
Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week)
flexibility home exercise

Primary Outcomes

Measure
Bone: Incident non-vertebral fractures
time frame: 36 months
Muscle: Functional decline (lower extremity function)
time frame: Baseline, 12, 24 and 36 months
Cardio-vascular: Systolic and diastolic blood pressure change
time frame: Baseline, 12, 24 and 36 months
Brain: Cognitive decline
time frame: Baseline, 12, 24 and 36 months
Immunity: Rate of infections
time frame: Baseline, and every 3 months up to 36 months

Secondary Outcomes

Measure
Bone: Incident hip fractures
time frame: 36 months
Bone: Incident total fractures
time frame: 36 months
Bone: Incident vertebral fractures
time frame: 36 months
Bone: Bone mineral density decrease at the lumbar spine and hip
time frame: Baseline, 12, 24, and 36 months
Muscle: Rate of falls
time frame: Assessed every 3 months over 36 months
Muscle: reaction time and grip strength
time frame: Baseline, 12,24,36 months
Muscle: Muscle mass decrease at upper and lower extremities
time frame: Baseline, 12,24,36 months
Muscle: Dual tasking 10-meter gait speed
time frame: Baseline, 12,24 and 36 months
Muscle/Bone: musculoskeletal pain
time frame: Baseline, 12,24, and 36 months
Cardio-vascular: Incident Hypertension
time frame: 36 months
Brain: mental health decline
time frame: Baseline, 12,24, and 36 months
Brain: Incident Depression
time frame: 36 months
Brain/Muscle: Dual tasking gait variability
time frame: Baseline, 12, 24 and 36 months
Immunity: Rate of upper respiratory infections / rate of flu-like illness
time frame: 36 months
Immunity: Incident severe infections that lead to hospital admission
time frame: 36 months
Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritis
time frame: Baseline, 12, 24 and 36 months
Cartilage/Bone: Rate of knee buckling
time frame: Baseline, 12,24,36 months
Cartilage/Bone: NSAID use / number of joints with pain
time frame: Baseline, 12, 24, 36 months
Dental: Decline in oral health
time frame: Baseline, 12,24 and 36 months
Dental: Tooth loss
time frame: 36 months
Gastro-Intestinal: rate of GI symptoms
time frame: Baseline, 12, 24 and 36 months
Glucose-Metabolic: Change in fasting glucose, insulin levels (QUICKI, HOMA index)
time frame: Baseline, 12,24,36 months
Glucose-Metabolic: Body composition
time frame: Baseline, 12, 24, 36 months
Kidney: Decline in kidney function
time frame: Baseline, 12, 24, and 36 months
Global Health: Quality of life
time frame: Every 6 months
Global Health: Incident disability regarding activities of daily living
time frame: Baseline, 12, 24 and 36 months
Global Health: Incident nursing home admission
time frame: 36 months
Global Health: Mortality
time frame: 36 months

Eligibility Criteria

Male or female participants at least 70 years old.

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)

Additional Information

Official title Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (Acronym: DO-HEALTH)
Principal investigator Heike Bischoff Ferrari, Prof MD
Description The 3 primary treatment comparisons are: 1. 2000 IU vitamin D per day compared to placebo (controlling for the other treatment strategies) 2. 1 gram of omega-3 fatty acids (EPA+DHA, ratio 1:2, from marine algae) compared to placebo (controlling for the other treatment strategies) 3. 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, 50% 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+). Even balance 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 participants 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/ website EC: http://ec.europa.eu/research/health/medical-research/human-development-and-ageing/projects/do-health_en.html
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by University of Zurich.