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

NCT ID: NCT01745263

Last Updated: 2018-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2157 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-20

Study Completion Date

2018-01-19

Brief Summary

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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

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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/

Conditions

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Improve Healthy Ageing in Seniors; Prevent Disease at Older Age

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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VitD-Omega3-StrengthExercise

Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Vitamin D3

Intervention Type DRUG

2000 IU/d

Omega 3 fatty acids

Intervention Type DRUG

Ratio EPA:DHA = 1:2

1 g/d

Strength Home Exercise

Intervention Type PROCEDURE

VitD-Omega3-FlexibilityExercise

Vitamin D3 (2000 IU/d); Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Vitamin D3

Intervention Type DRUG

2000 IU/d

Omega 3 fatty acids

Intervention Type DRUG

Ratio EPA:DHA = 1:2

1 g/d

Flexibility Home Exercise

Intervention Type PROCEDURE

Placebo-Omega3-StrengthExercise

Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Strength Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Omega 3 fatty acids

Intervention Type DRUG

Ratio EPA:DHA = 1:2

1 g/d

Strength Home Exercise

Intervention Type PROCEDURE

Placebo-Omega3-FlexibilityExercise

Placebo Vitamin D3; Omega-3 fatty acids (1 g/d); Flexibility Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Omega 3 fatty acids

Intervention Type DRUG

Ratio EPA:DHA = 1:2

1 g/d

Flexibility Home Exercise

Intervention Type PROCEDURE

VitD-Placebo-StrengthExercise

Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Vitamin D3

Intervention Type DRUG

2000 IU/d

Strength Home Exercise

Intervention Type PROCEDURE

VitD-Placebo-FlexiblityExercise

Vitamin D3 (2000 IU/d); Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Vitamin D3

Intervention Type DRUG

2000 IU/d

Flexibility Home Exercise

Intervention Type PROCEDURE

Placebo-Placebo-StrengthExercise

Placebo Vitamin D3; Placebo Omega-3 fatty acids; Strength Home Exercise (3\*30 minutes/week)

Group Type ACTIVE_COMPARATOR

Strength Home Exercise

Intervention Type PROCEDURE

Placebo-Placebo-FlexibilityExercise

Placebo Vitamin D3; Placebo Omega-3 fatty acids; Flexibility Home Exercise (3\*30 minutes/week)

Group Type SHAM_COMPARATOR

Flexibility Home Exercise

Intervention Type PROCEDURE

Interventions

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Vitamin D3

2000 IU/d

Intervention Type DRUG

Omega 3 fatty acids

Ratio EPA:DHA = 1:2

1 g/d

Intervention Type DRUG

Strength Home Exercise

Intervention Type PROCEDURE

Flexibility Home Exercise

Intervention Type PROCEDURE

Other Intervention Names

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Cholecalciferol Eicosapentaenoic acid AND Docosahexaenoic acid

Eligibility Criteria

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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").
Minimum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Recruitment Partners

UNKNOWN

Sponsor Role collaborator

University of Geneva, Switzerland

OTHER

Sponsor Role collaborator

University of Basel

OTHER

Sponsor Role collaborator

University Hospital, Toulouse, France (Prof. Bruno Vellas, MD)

UNKNOWN

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Medical University Innsbruck

OTHER

Sponsor Role collaborator

University of Coimbra, Portugal (Prof. José daSilva, MD)

UNKNOWN

Sponsor Role collaborator

Other University Partners

UNKNOWN

Sponsor Role collaborator

University of Sheffield

OTHER

Sponsor Role collaborator

University of Manchester, UK (Prof. David Felson, MD MPH)

UNKNOWN

Sponsor Role collaborator

Max Rubner University, Germany (Prof. Bernhard Watzl, PhD)

UNKNOWN

Sponsor Role collaborator

Technische Universität Dresden

OTHER

Sponsor Role collaborator

Impact Partner

UNKNOWN

Sponsor Role collaborator

International Osteoporosis Foundation (IOF; Prof. John Kanis, MD)

UNKNOWN

Sponsor Role collaborator

SME Partners

UNKNOWN

Sponsor Role collaborator

Ferrari Data Solution

OTHER

Sponsor Role collaborator

Gut Pictures, Switzerland (Benno Gut; animated exercise video)

UNKNOWN

Sponsor Role collaborator

NOVAMEN, France (Sandrine Rival; logistic management partner)

UNKNOWN

Sponsor Role collaborator

Pharmalys, UK (Marieme Ba; monitoring partner)

UNKNOWN

Sponsor Role collaborator

Industry Partners

UNKNOWN

Sponsor Role collaborator

DSM Nutritional Products (Dr. Elisabeth Stöcklin PhD, Dr. Manfred Eggersdorfer PhD)

UNKNOWN

Sponsor Role collaborator

Nestlé (Michaela Höhne PhD, Irène Corthesy PhD)

UNKNOWN

Sponsor Role collaborator

Roche Diagnostics GmbH

INDUSTRY

Sponsor Role collaborator

European Commission

OTHER

Sponsor Role collaborator

Further collaborators and advisors at website do-health.eu

UNKNOWN

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Heike Bischoff-Ferrari

Director, Centre on Aging and Mobility

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heike Bischoff Ferrari, Prof MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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University of Innsbruck

Innsbruck, , Austria

Site Status

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

Toulouse, , France

Site Status

Charité Berlin

Berlin, , Germany

Site Status

University of Coimbra - Clínica Universitária de Reumatologia

Coimbra, , Portugal

Site Status

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

Zurich, Canton of Zurich, Switzerland

Site Status

Basel University

Basel, , Switzerland

Site Status

Hôpitaux Universitaires de Genève

Geneva, , Switzerland

Site Status

Countries

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Austria France Germany Portugal Switzerland

References

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Kistler-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.

Reference Type DERIVED
PMID: 40095212 (View on PubMed)

de 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.

Reference Type DERIVED
PMID: 39614147 (View on PubMed)

Gaengler 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.

Reference Type DERIVED
PMID: 38199870 (View on PubMed)

Gagesch 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.

Reference Type DERIVED
PMID: 37543639 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35821820 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35487733 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35236290 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33170239 (View on PubMed)

Related Links

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Other Identifiers

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DO-HEALTH

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

KEK-ZH-2012-0249

Identifier Type: -

Identifier Source: org_study_id

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