Improve Healthy Ageing in Seniors; Prevent Disease at Older AgePhase 3DO-HEALTHNCT01745263
DO-HEALTH / Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial
A Phase 3 study testing Vitamin D3, Omega 3 fatty acids and Strength Home Exercise in people with Improve Healthy Ageing in Seniors; Prevent Disease at Older Age, run by University of Zurich at 7 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and olderHealthy volunteers can take part
- Conditions the study is for
- Improve Healthy Ageing in Seniors; Prevent Disease at Older Age
- What is being tested?
- Vitamin D3, Omega 3 fatty acids and Strength Home Exercise
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,157 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 20 Dec 2012to 19 Jan 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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").
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Switzerland3 sites
Basel University
Basel
Hôpitaux Universitaires de Genève
Geneva
Centre on Aging and Mobility, University of Zurich and City Hospital Waid
Zurich, Canton of Zurich, 8091
France1 site
University of Toulouse - Centre de Recherche - Gérontopôle Hôpital La Grave
Toulouse
Portugal1 site
University of Coimbra - Clínica Universitária de Reumatologia
Coimbra
About this study
Official title: 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.
Read more
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/
Read the 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/
- Being tested
- Vitamin D3, Omega 3 fatty acids, Strength Home Exercise, Flexibility Home Exercise
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3Drug
Also called Cholecalciferol
2000 IU/d
Omega 3 fatty acidsDrug
Also called Eicosapentaenoic acid AND Docosahexaenoic acid
Ratio EPA:DHA = 1:2
1 g/d
Strength Home ExerciseProcedure or surgery
Flexibility Home ExerciseProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| VitD-Omega3-StrengthExercise | Active comparator | Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week) Receives: Drug: Vitamin D3; Drug: Omega 3 fatty acids; Procedure: Strength Home Exercise |
| VitD-Omega3-FlexibilityExercise | Active comparator | Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week) Receives: Drug: Vitamin D3; Drug: Omega 3 fatty acids; Procedure: Flexibility Home Exercise |
| Placebo-Omega3-StrengthExercise | Active comparator | Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week) Receives: Drug: Omega 3 fatty acids; Procedure: Strength Home Exercise |
| Placebo-Omega3-FlexibilityExercise | Active comparator | Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week) Receives: Drug: Omega 3 fatty acids; Procedure: Flexibility Home Exercise |
| VitD-Placebo-StrengthExercise | Active comparator | Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week) Receives: Drug: Vitamin D3; Procedure: Strength Home Exercise |
| VitD-Placebo-FlexiblityExercise | Active comparator | Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week) Receives: Drug: Vitamin D3; Procedure: Flexibility Home Exercise |
| Placebo-Placebo-StrengthExercise | Active comparator | Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week) Receives: Procedure: Strength Home Exercise |
| Placebo-Placebo-FlexibilityExercise | Sham comparator | Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week) Receives: Procedure: Flexibility Home Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone: Incident non-vertebral fractures over 36 months
Confirmed by medical and/or x-ray reports
Measured: over 36 months
Muscle: Functional decline (lower extremity function)
Measured with the SPPB (short physical performance test battery)
Measured: Baseline, 12, 24 and 36 months
Cardio-vascular: Systolic and diastolic blood pressure change
Standardized blood pressure assessment in sitting position
Measured: Baseline, 12, 24 and 36 months
Brain: Cognitive decline
Montreal Cognitive Assessment (MoCA)
Measured: Baseline, 12, 24 and 36 months
Immunity: Rate of any infections
3-monthly incident infection protocol
Measured: Baseline, and every 3 months up to 36 months
Secondary outcomes (28)
Bone: Incident hip fractures
Based on medical records and/or x-ray reports
Measured: 36 months
Bone: Incident total fractures
Combined non-vertebral and vertebral fractures among subgroup of 1502 participants with DXA vertebral morphometry assessment
Measured: 36 months
Bone: Incident vertebral fractures
Based on DXA vertebral morphometry among subset of 1502 participants
Measured: 36 months
Bone: Bone mineral density decrease at the lumbar spine and hip
Assessed in a subset of 1502 participants with DXA measurements
Measured: Baseline, 12, 24, and 36 months
Muscle: Rate of falls
Any low trauma fall, injurious fall
Measured: Assessed every 3 months over 36 months
Muscle: reaction time and grip strength
Reaction time will be assessed with the repeated sit-to-stand test; grip strength will be assessed with the Martin Vigorimeter
Measured: Baseline, 12,24,36 months
Muscle: Muscle mass decrease at upper and lower extremities
Subset of 1502 participants with DXA measurements
Measured: Baseline, 12,24,36 months
Muscle: Dual tasking 10-meter gait speed
Measured: Baseline, 12,24 and 36 months
Muscle/Bone: musculoskeletal pain
Assessed with the McGill questionnaire
Measured: Baseline, 12,24, and 36 months
Cardio-vascular: Incident Hypertension
Measured: 36 months
Brain: mental health decline
Assessed with Geriatric Depression Scale
Measured: Baseline, 12,24, and 36 months
Brain: Incident Depression
Measured: 36 months
Brain/Muscle: Dual tasking gait variability
Subset of 250 participants
Measured: Baseline, 12, 24 and 36 months
Immunity: Rate of upper respiratory infections / rate of flu-like illness
Assessed with infection protocol every 3 months
Measured: 36 months
Immunity: Incident severe infections that lead to hospital admission
Measured: 36 months
Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritis
Assessed with the KOOS questionnaire. Knee OA assessment with modified ACR criteria.
Measured: Baseline, 12, 24 and 36 months
Cartilage/Bone: Rate of knee buckling
Questionnaire-based.
Measured: Baseline, 12,24,36 months
Cartilage/Bone: NSAID use / number of joints with pain
Assessed by questionnaire and homunculus figure
Measured: Baseline, 12, 24, 36 months
Dental: Decline in oral health
Assessed with questionnaire.
Measured: Baseline, 12,24 and 36 months
Dental: Tooth loss
Assessed by tooth count at every clinical visit
Measured: 36 months
Gastro-Intestinal: rate of GI symptoms
Assessed with ROME III questionnaire.
Measured: Baseline, 12, 24 and 36 months
Glucose-Metabolic: Change in fasting glucose, insulin levels (QUICKI, HOMA index)
Laboratory measures at the Central DO-HEALTH Laboratory (Institute of Clinical Chemistry at the University Hospital Zurich)
Measured: Baseline, 12,24,36 months
Glucose-Metabolic: Body composition
Subset of 1502 participants with DXA measurements
Measured: Baseline, 12, 24, 36 months
Kidney: Decline in kidney function
Blood creatinine levels and estimated glomerular filtration rate
Measured: Baseline, 12, 24, and 36 months
Global Health: Quality of life
Assessed with questionnaire (EuroQuol).
Measured: Every 6 months
Global Health: Incident disability regarding activities of daily living
Assessed with HAQ-PROMIS questionnaire
Measured: Baseline, 12, 24 and 36 months
Global Health: Incident nursing home admission
Measured: 36 months
Global Health: Mortality
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study start20 Dec 2012
- Primary completion17 Nov 2017
- Study completion19 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Improve Healthy Ageing in Seniors; Prevent Disease at Older AgeStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,157 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Recruitment Partners, University of Geneva, Switzerland, University of Basel, University Hospital, Toulouse, France (Prof. Bruno Vellas, MD), Charite University, Berlin, Germany, Medical University Innsbruck, University of Coimbra, Other University Partners, University of Sheffield, University of Manchester, UK (Prof. David Felson, MD MPH), Max Rubner University, Germany (Prof. Bernhard Watzl, PhD), Technische Universität Dresden, Impact Partner, International Osteoporosis Foundation (IOF; Prof. John Kanis, MD), SME Partners, Ferrari Data Solution, Gut Pictures, Switzerland (Benno Gut; animated exercise video), NOVAMEN, France (Sandrine Rival; logistic management partner), Pharmalys, UK (Marieme Ba; monitoring partner), Industry Partners, DSM Nutritional Products (Dr. Elisabeth Stöcklin PhD, Dr. Manfred Eggersdorfer PhD), Nestlé (Michaela Höhne PhD, Irène Corthesy PhD), Roche Diagnostics GmbH, European Commission, Further collaborators and advisors at website do-health.eu
- Responsible party
- Principal investigator, Heike Bischoff-Ferrari, University of Zurich
- Investigators
- Heike Bischoff Ferrari, Prof MD, Principal investigator, "Centre on Aging and Mobility" University of Zurich, University Hospital Zurich and City Hospital Waid.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745263
- Sponsor's protocol ID
- KEK-ZH-2012-0249
- Other IDs
- DO-HEALTH
- Acronym
- DO-HEALTH
- Status last verified
- Aug 2018
- First submitted
- 6 Dec 2012
- Last updated
- 9 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rosler W, Kistler-Fischbacher M, Gangler S, Manz MG, Reto KW, Orav JE, Dawson-Hughes B, Ryan J, Belsky DW, Horvath S, Willett WC, Wieczorek M, Bischoff-Ferrari HA. Trajectories of physical function and biological aging in generally healthy older adults with and without incident invasive cancer over a three-year follow-up: findings from the DO-HEALTH study. NPJ Aging. 2026 Mar 23;12(1):99. doi: 10.1038/s41514-026-00360-2.
PubMed 41872206Wieczorek M, Funk J, Mattle M, Gangler S, Egli A, Kressig RW, Manz MG, Bischoff-Ferrari HA; DO-HEALTH Research group. Association between hemoglobin levels and mild cognitive impairment in generally healthy European community-dwelling older adults: a 3-year prospective analysis of the DO-HEALTH trial. Am J Clin Nutr. 2026 Feb;123(2):101114. doi: 10.1016/j.ajcnut.2025.11.005. Epub 2025 Nov 13.
PubMed 41241003Kistler-Fischbacher M, Gohar G, de Godoi Rezende Costa Molino C, Geiling K, Meyer-Heim T, Kressig RW, Orav EJ, Vellas B, Guyonnet S, da Sliva JAP, Rizzoli R, Armbrecht G, Steinhagen-Thiessen E, Egli A, Bischoff-Ferrari HA. Cognitive function in generally healthy adults age 70 years and older in the 5-country DO-HEALTH study: MMSE and MoCA scores by sex, education and country. Aging Clin Exp Res. 2025 Mar 17;37(1):88. doi: 10.1007/s40520-025-02946-4.
PubMed 40095212de Godoi Rezende Costa Molino C, Forster CK, Wieczorek M, Orav EJ, Kressig RW, Vellas B, Egli A, Freystaetter G, Bischoff-Ferrari HA; DO-HEALTH Research Group. Association of fall risk-increasing drugs with falls in generally healthy older adults: a 3-year prospective observational study of the DO-HEALTH trial. BMC Geriatr. 2024 Nov 29;24(1):980. doi: 10.1186/s12877-024-05557-2.
PubMed 39614147Kistler-Fischbacher M, Armbrecht G, Gangler S, Theiler R, Rizzoli R, Dawson-Hughes B, Kanis JA, Hofbauer LC, Schimmer RC, Vellas B, Da Silva JAP, John OE, Kressig RW, Andreas E, Lang W, Wanner GA, Bischoff-Ferrari HA; DO-HEALTH Research Group. Effects of vitamin D3, omega-3s, and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial. J Bone Miner Res. 2024 Jul 23;39(6):661-671. doi: 10.1093/jbmr/zjae054.
PubMed 38613445Gaengler S, Sadlon A, De Godoi Rezende Costa Molino C, Willett WC, Manson JE, Vellas B, Steinhagen-Thiessen E, Von Eckardstein A, Ruschitzka F, Rizzoli R, da Silva JAP, Kressig RW, Kanis J, Orav EJ, Egli A, Bischoff-Ferrari HA. Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial. J Nutr Health Aging. 2024 Feb;28(2):100037. doi: 10.1016/j.jnha.2024.100037. Epub 2024 Jan 9.
PubMed 38199870Gagesch M, Wieczorek M, Abderhalden LA, Lang W, Freystaetter G, Armbrecht G, Kressig RW, Vellas B, Rizzoli R, Blauth M, Orav EJ, Egli A, Bischoff-Ferrari HA. Grip strength cut-points from the Swiss DO-HEALTH population. Eur Rev Aging Phys Act. 2023 Aug 5;20(1):13. doi: 10.1186/s11556-023-00323-6.
PubMed 37543639Bischoff-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.
PubMed 35821820de 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.
PubMed 35487733Schietzel 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.
PubMed 35236290Bischoff-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.
PubMed 33170239
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (Acronym: DO-HEALTH)
- ClinicalTrials.gov ID
- NCT01745263
- Acronym / sponsor ID
- DO-HEALTH / KEK-ZH-2012-0249
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,157 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Recruitment Partners, University of Geneva, Switzerland, University of Basel, University Hospital, Toulouse, France (Prof. Bruno Vellas, MD), Charite University, Berlin, Germany, Medical University Innsbruck, University of Coimbra, Other University Partners, University of Sheffield, University of Manchester, UK (Prof. David Felson, MD MPH), Max Rubner University, Germany (Prof. Bernhard Watzl, PhD), Technische Universität Dresden, Impact Partner, International Osteoporosis Foundation (IOF; Prof. John Kanis, MD), SME Partners, Ferrari Data Solution, Gut Pictures, Switzerland (Benno Gut; animated exercise video), NOVAMEN, France (Sandrine Rival; logistic management partner), Pharmalys, UK (Marieme Ba; monitoring partner), Industry Partners, DSM Nutritional Products (Dr. Elisabeth Stöcklin PhD, Dr. Manfred Eggersdorfer PhD), Nestlé (Michaela Höhne PhD, Irène Corthesy PhD), Roche Diagnostics GmbH, European Commission, Further collaborators and advisors at website do-health.eu
- Study start
- 20 Dec 2012 (actual)
- Primary completion
- 17 Nov 2017 (actual)
- Study completion
- 19 Jan 2018 (actual)
- First posted
- 10 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| VitD-Omega3-StrengthExercise | Active comparator | Drug: Vitamin D3, Drug: Omega 3 fatty acids, Procedure: Strength Home ExerciseVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week) |
| VitD-Omega3-FlexibilityExercise | Active comparator | Drug: Vitamin D3, Drug: Omega 3 fatty acids, Procedure: Flexibility Home ExerciseVitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week) |
| Placebo-Omega3-StrengthExercise | Active comparator | Drug: Omega 3 fatty acids, Procedure: Strength Home ExercisePlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3*30 minutes/week) |
| Placebo-Omega3-FlexibilityExercise | Active comparator | Drug: Omega 3 fatty acids, Procedure: Flexibility Home ExercisePlacebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3*30 minutes/week) |
| VitD-Placebo-StrengthExercise | Active comparator | Drug: Vitamin D3, Procedure: Strength Home ExerciseVitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week) |
| VitD-Placebo-FlexiblityExercise | Active comparator | Drug: Vitamin D3, Procedure: Flexibility Home ExerciseVitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week) |
| Placebo-Placebo-StrengthExercise | Active comparator | Procedure: Strength Home ExercisePlacebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3*30 minutes/week) |
| Placebo-Placebo-FlexibilityExercise | Sham comparator | Procedure: Flexibility Home ExercisePlacebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3*30 minutes/week) |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3Also: Cholecalciferol2000 IU/d | Drug | VitD-Omega3-FlexibilityExercise, VitD-Omega3-StrengthExercise, VitD-Placebo-FlexiblityExercise, VitD-Placebo-StrengthExercise |
| Omega 3 fatty acidsAlso: Eicosapentaenoic acid AND Docosahexaenoic acidRatio EPA:DHA = 1:2 1 g/d | Drug | Placebo-Omega3-FlexibilityExercise, Placebo-Omega3-StrengthExercise, VitD-Omega3-FlexibilityExercise, VitD-Omega3-StrengthExercise |
| Strength Home Exercise | Procedure or surgery | Placebo-Omega3-StrengthExercise, Placebo-Placebo-StrengthExercise, VitD-Omega3-StrengthExercise, VitD-Placebo-StrengthExercise |
| Flexibility Home Exercise | Procedure or surgery | Placebo-Omega3-FlexibilityExercise, Placebo-Placebo-FlexibilityExercise, VitD-Omega3-FlexibilityExercise, VitD-Placebo-FlexiblityExercise |
Primary outcome
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)
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)
Immunity: Rate of any infections
Time frame: Baseline, and every 3 months up to 36 months
3-monthly incident infection protocol
28 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Derived from this study: PubMed 41872206Rosler W, Kistler-Fischbacher M, Gangler S, Manz MG, Reto KW, Orav JE, Dawson-Hughes B, Ryan J, Belsky DW, Horvath S, Willett WC, Wieczorek M, Bischoff-Ferrari HA. Trajectories of physical function and biological aging in generally healthy older adults with and without incident invasive cancer over a three-year follow-up: findings from the DO-HEALTH study. NPJ Aging. 2026 Mar 23;12(1):99. doi: 10.1038/s41514-026-00360-2.
- Derived from this study: PubMed 41241003Wieczorek M, Funk J, Mattle M, Gangler S, Egli A, Kressig RW, Manz MG, Bischoff-Ferrari HA; DO-HEALTH Research group. Association between hemoglobin levels and mild cognitive impairment in generally healthy European community-dwelling older adults: a 3-year prospective analysis of the DO-HEALTH trial. Am J Clin Nutr. 2026 Feb;123(2):101114. doi: 10.1016/j.ajcnut.2025.11.005. Epub 2025 Nov 13.
- Derived from this study: PubMed 40095212Kistler-Fischbacher M, Gohar G, de Godoi Rezende Costa Molino C, Geiling K, Meyer-Heim T, Kressig RW, Orav EJ, Vellas B, Guyonnet S, da Sliva JAP, Rizzoli R, Armbrecht G, Steinhagen-Thiessen E, Egli A, Bischoff-Ferrari HA. Cognitive function in generally healthy adults age 70 years and older in the 5-country DO-HEALTH study: MMSE and MoCA scores by sex, education and country. Aging Clin Exp Res. 2025 Mar 17;37(1):88. doi: 10.1007/s40520-025-02946-4.
- Derived from this study: PubMed 39614147de Godoi Rezende Costa Molino C, Forster CK, Wieczorek M, Orav EJ, Kressig RW, Vellas B, Egli A, Freystaetter G, Bischoff-Ferrari HA; DO-HEALTH Research Group. Association of fall risk-increasing drugs with falls in generally healthy older adults: a 3-year prospective observational study of the DO-HEALTH trial. BMC Geriatr. 2024 Nov 29;24(1):980. doi: 10.1186/s12877-024-05557-2.
- Derived from this study: PubMed 38613445Kistler-Fischbacher M, Armbrecht G, Gangler S, Theiler R, Rizzoli R, Dawson-Hughes B, Kanis JA, Hofbauer LC, Schimmer RC, Vellas B, Da Silva JAP, John OE, Kressig RW, Andreas E, Lang W, Wanner GA, Bischoff-Ferrari HA; DO-HEALTH Research Group. Effects of vitamin D3, omega-3s, and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial. J Bone Miner Res. 2024 Jul 23;39(6):661-671. doi: 10.1093/jbmr/zjae054.
- Derived from this study: PubMed 38199870Gaengler S, Sadlon A, De Godoi Rezende Costa Molino C, Willett WC, Manson JE, Vellas B, Steinhagen-Thiessen E, Von Eckardstein A, Ruschitzka F, Rizzoli R, da Silva JAP, Kressig RW, Kanis J, Orav EJ, Egli A, Bischoff-Ferrari HA. Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial. J Nutr Health Aging. 2024 Feb;28(2):100037. doi: 10.1016/j.jnha.2024.100037. Epub 2024 Jan 9.
- Derived from this study: PubMed 37543639Gagesch M, Wieczorek M, Abderhalden LA, Lang W, Freystaetter G, Armbrecht G, Kressig RW, Vellas B, Rizzoli R, Blauth M, Orav EJ, Egli A, Bischoff-Ferrari HA. Grip strength cut-points from the Swiss DO-HEALTH population. Eur Rev Aging Phys Act. 2023 Aug 5;20(1):13. doi: 10.1186/s11556-023-00323-6.
- Derived from this study: PubMed 35821820Bischoff-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.
- Derived from this study: PubMed 35487733de 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.
- Derived from this study: PubMed 35236290Schietzel 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.
- Derived from this study: PubMed 33170239Bischoff-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.
- European Commission project link for DO-HEALTHLink provided by the sponsor.
- Website DO-HEALTH ConsortiumLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heike Bischoff Ferrari, Prof MD principal investigator
"Centre on Aging and Mobility" University of Zurich, University Hospital Zurich and City Hospital Waid.
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D3, Omega 3 fatty acids and Strength Home Exercise in people with Improve Healthy Ageing in Seniors; Prevent Disease at Older Age, run by University of Zurich at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Switzerland, Austria, France, Germany, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone: Incident non-vertebral fractures over 36 months (time frame: over 36 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01745263, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2018.