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

Phase 3
Completed
Conditions
Improve Healthy Ageing in Seniors; Prevent Disease at Older Age
Interventions
Procedure: Strength Home Exercise
Procedure: Flexibility Home Exercise
Registration Number
NCT01745263
Lead Sponsor
University of Zurich
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:

1. 2000 IU vitamin D per day compared to placebo (controlling for the other treatment strategies)

2. 1 g 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, 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/

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2157
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
VitD-Omega3-StrengthExerciseStrength Home ExerciseVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)
Placebo-Placebo-StrengthExerciseStrength Home ExercisePlacebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)
VitD-Omega3-FlexibilityExerciseFlexibility Home ExerciseVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)
Placebo-Omega3-StrengthExerciseStrength Home ExercisePlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)
Placebo-Placebo-FlexibilityExerciseFlexibility Home ExercisePlacebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)
VitD-Placebo-StrengthExerciseStrength Home ExerciseVitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)
Placebo-Omega3-FlexibilityExerciseFlexibility Home ExercisePlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)
VitD-Placebo-FlexiblityExerciseFlexibility Home ExerciseVitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)
VitD-Omega3-StrengthExerciseVitamin D3Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)
VitD-Omega3-FlexibilityExerciseVitamin D3Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)
Placebo-Omega3-StrengthExerciseOmega 3 fatty acidsPlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)
Placebo-Omega3-FlexibilityExerciseOmega 3 fatty acidsPlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)
VitD-Placebo-StrengthExerciseVitamin D3Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)
VitD-Placebo-FlexiblityExerciseVitamin D3Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)
VitD-Omega3-StrengthExerciseOmega 3 fatty acidsVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)
VitD-Omega3-FlexibilityExerciseOmega 3 fatty acidsVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)
Primary Outcome Measures
NameTimeMethod
Cardio-vascular: Systolic and diastolic blood pressure changeBaseline, 12, 24 and 36 months

Standardized blood pressure assessment in sitting position

Brain: Cognitive declineBaseline, 12, 24 and 36 months

Montreal Cognitive Assessment (MoCA)

Bone: Incident non-vertebral fractures over 36 monthsover 36 months

Confirmed by medical and/or x-ray reports

Muscle: Functional decline (lower extremity function)Baseline, 12, 24 and 36 months

Measured with the SPPB (short physical performance test battery)

Immunity: Rate of any infectionsBaseline, and every 3 months up to 36 months

3-monthly incident infection protocol

Secondary Outcome Measures
NameTimeMethod
Cartilage/Bone: NSAID use / number of joints with painBaseline, 12, 24, 36 months

Assessed by questionnaire and homunculus figure

Global Health: Quality of lifeEvery 6 months

Assessed with questionnaire (EuroQuol).

Global Health: Incident nursing home admission36 months
Global Health: Mortality36 months
Bone: Incident total fractures36 months

Combined non-vertebral and vertebral fractures among subgroup of 1502 participants with DXA vertebral morphometry assessment

Bone: Incident hip fractures36 months

Based on medical records and/or x-ray reports

Muscle: reaction time and grip strengthBaseline, 12,24,36 months

Reaction time will be assessed with the repeated sit-to-stand test; grip strength will be assessed with the Martin Vigorimeter

Muscle: Muscle mass decrease at upper and lower extremitiesBaseline, 12,24,36 months

Subset of 1502 participants with DXA measurements

Muscle/Bone: musculoskeletal painBaseline, 12,24, and 36 months

Assessed with the McGill questionnaire

Bone: Incident vertebral fractures36 months

Based on DXA vertebral morphometry among subset of 1502 participants

Muscle: Dual tasking 10-meter gait speedBaseline, 12,24 and 36 months
Bone: Bone mineral density decrease at the lumbar spine and hipBaseline, 12, 24, and 36 months

Assessed in a subset of 1502 participants with DXA measurements

Muscle: Rate of fallsAssessed every 3 months over 36 months

Any low trauma fall, injurious fall

Brain: mental health declineBaseline, 12,24, and 36 months

Assessed with Geriatric Depression Scale

Brain/Muscle: Dual tasking gait variabilityBaseline, 12, 24 and 36 months

Subset of 250 participants

Brain: Incident Depression36 months
Immunity: Incident severe infections that lead to hospital admission36 months
Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritisBaseline, 12, 24 and 36 months

Assessed with the KOOS questionnaire. Knee OA assessment with modified ACR criteria.

Cardio-vascular: Incident Hypertension36 months
Immunity: Rate of upper respiratory infections / rate of flu-like illness36 months

Assessed with infection protocol every 3 months

Cartilage/Bone: Rate of knee bucklingBaseline, 12,24,36 months

Questionnaire-based.

Gastro-Intestinal: rate of GI symptomsBaseline, 12, 24 and 36 months

Assessed with ROME III questionnaire.

Dental: Decline in oral healthBaseline, 12,24 and 36 months

Assessed with questionnaire.

Dental: Tooth loss36 months

Assessed by tooth count at every clinical visit

Glucose-Metabolic: Body compositionBaseline, 12, 24, 36 months

Subset of 1502 participants with DXA measurements

Kidney: Decline in kidney functionBaseline, 12, 24, and 36 months

Blood creatinine levels and estimated glomerular filtration rate

Glucose-Metabolic: Change in fasting glucose, insulin levels (QUICKI, HOMA index)Baseline, 12,24,36 months

Laboratory measures at the Central DO-HEALTH Laboratory (Institute of Clinical Chemistry at the University Hospital Zurich)

Global Health: Incident disability regarding activities of daily livingBaseline, 12, 24 and 36 months

Assessed with HAQ-PROMIS questionnaire

Trial Locations

Locations (7)

University of Toulouse - Centre de Recherche - Gérontopôle Hôpital La Grave

🇫🇷

Toulouse, France

Charité Berlin

🇩🇪

Berlin, Germany

University of Coimbra - Clínica Universitária de Reumatologia

🇵🇹

Coimbra, Portugal

Centre on Aging and Mobility, University of Zurich and City Hospital Waid

🇨🇭

Zurich, ZH, Switzerland

Hôpitaux Universitaires de Genève

🇨🇭

Geneva, Switzerland

University of Innsbruck

🇦🇹

Innsbruck, Austria

Basel University

🇨🇭

Basel, Switzerland

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