Improve Healthy Ageing in Seniors; Prevent Disease at Older Age Clinical Trial
— DO-HEALTHOfficial title:
Vitamin D3 - Omega3 - Home Exercise - Healthy Ageing and Longevity Trial (Acronym: DO-HEALTH)
| Verified date | August 2018 |
| Source | University of Zurich |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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/
| Status | Completed |
| Enrollment | 2157 |
| Est. completion date | January 19, 2018 |
| Est. primary completion date | November 17, 2017 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 70 Years and older |
| Eligibility |
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"). |
| Country | Name | City | State |
|---|---|---|---|
| Austria | University of Innsbruck | Innsbruck | |
| France | University of Toulouse - Centre de Recherche - Gérontopôle Hôpital La Grave | Toulouse | |
| Germany | Charité Berlin | Berlin | |
| Portugal | University of Coimbra - Clínica Universitária de Reumatologia | Coimbra | |
| Switzerland | Basel University | Basel | |
| Switzerland | Hôpitaux Universitaires de Genève | Geneva | |
| Switzerland | Centre on Aging and Mobility, University of Zurich and City Hospital Waid | Zurich | ZH |
| Lead Sponsor | Collaborator |
|---|---|
| University of Zurich | Charite University, Berlin, Germany, DSM Nutritional Products (Dr. Elisabeth Stöcklin PhD, Dr. Manfred Eggersdorfer PhD), Ferrari Data Solutions GmBH, Switzerland (Stephen M. Ferrari; direct data entry platform), Funding within Framework 7 research program of the European Commission (project 278588), Further collaborators and advisors at website do-health.eu, Gut Pictures, Switzerland (Benno Gut; animated exercise video), Impact Partner, Industry Partners, International Osteoporosis Foundation (IOF; Prof. John Kanis, MD), Max Rubner University, Germany (Prof. Bernhard Watzl, PhD), Medical University Innsbruck, Nestlé (Michaela Höhne PhD, Irène Corthesy PhD), NOVAMEN, France (Sandrine Rival; logistic management partner), Other University Partners, Pharmalys, UK (Marieme Ba; monitoring partner), Recruitment Partners, Roche Diagnostics, SME Partners, Technische Universität Dresden, University Hospital, Toulouse, France (Prof. Bruno Vellas, MD), University of Basel, University of Coimbra, Portugal (Prof. José daSilva, MD), University of Geneva, Switzerland, University of Manchester, UK (Prof. David Felson, MD MPH), University of Sheffield |
Austria, France, Germany, Portugal, Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Biomarker endpoints | Baseline, 12, 24, and 36 months | ||
| Other | Bone: Incident repeat fractures | Any repeat non-vertebral fractures in all participants, vertebral fractures and total fractures among subset of 1502 seniors with yearly DXA measurements | 36 months | |
| Other | BONE: Functional recovery after long bone fracture | 36 months | ||
| Other | Muscle: Incident sarcopenia / incident frailty / decline in physical function | Incident sarcopenia (among subset of 1502 seniors with yearly DXA measurements), incident frailty (questionnaire), decline in physical activity (questionnaire) | 36 months | |
| Other | Cardio-vascular: Major cardio-vascular events | Major cardiovascular events as a composite endpoint (any event: myocardial infarction, stroke, revascularization procedures of CABG and PCI, incident congestive heart disease, cardiovascular mortality); individual endpoints: myocardial infarction, stroke, incident congestive heart disease, and cardiovascular mortality (assessed every 3 months over 36 months) | 36 months | |
| Other | Brain: incident dementia | 36 months | ||
| Other | Immunity: Incident cancer / rate of implant infections / rate of gastro-intestinal infections | Incident cancer (any cancer, gastro-intestinal, breast cancer in women, prostate cancer in men); rate of implant infections after total hip or knee replacement (due to fracture or osteoarthritis); rate of gastro-intestinal infections | 36 months | |
| Other | Cartilage/bone: Incident osteoarthritis | Incident symptomatic knee osteoarthritis; incident symptomatic hip osteoarthritis, incident symptomatic hand osteoarthritis; composite endpoint: incident symptomatic knee, hip or hand osteoarthritis; severity of hip pain in those with prevalent symptomatic hip osteoarthritis, severity of hand pain in those with prevalent symptomatic hand osteoarthritis | Baseline, 12, 24, and 36 months | |
| Other | Adherence laboratory | Serum 25(OH)D concentrations (measured both by an automated assay and HPLCMS/MS) and plasma PUFA concentrations (EPA, AA, DPA, DHA; measured by a sensitive and selective assay based on gas chromatography coupled to mass spectrometry detection (GC-MS)) in all participants | Baseline, 12, 24, and 36 months | |
| Primary | Bone: Incident non-vertebral fractures over 36 months | Confirmed by medical and/or x-ray reports | over 36 months | |
| Primary | Muscle: Functional decline (lower extremity function) | Measured with the SPPB (short physical performance test battery) | Baseline, 12, 24 and 36 months | |
| Primary | Cardio-vascular: Systolic and diastolic blood pressure change | Standardized blood pressure assessment in sitting position | Baseline, 12, 24 and 36 months | |
| Primary | Brain: Cognitive decline | Montreal Cognitive Assessment (MoCA) | Baseline, 12, 24 and 36 months | |
| Primary | Immunity: Rate of any infections | 3-monthly incident infection protocol | Baseline, and every 3 months up to 36 months | |
| Secondary | Bone: Incident hip fractures | Based on medical records and/or x-ray reports | 36 months | |
| Secondary | Bone: Incident total fractures | Combined non-vertebral and vertebral fractures among subgroup of 1502 participants with DXA vertebral morphometry assessment | 36 months | |
| Secondary | Bone: Incident vertebral fractures | Based on DXA vertebral morphometry among subset of 1502 participants | 36 months | |
| Secondary | Bone: Bone mineral density decrease at the lumbar spine and hip | Assessed in a subset of 1502 participants with DXA measurements | Baseline, 12, 24, and 36 months | |
| Secondary | Muscle: Rate of falls | Any low trauma fall, injurious fall | Assessed every 3 months over 36 months | |
| Secondary | 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 | Baseline, 12,24,36 months | |
| Secondary | Muscle: Muscle mass decrease at upper and lower extremities | Subset of 1502 participants with DXA measurements | Baseline, 12,24,36 months | |
| Secondary | Muscle: Dual tasking 10-meter gait speed | Baseline, 12,24 and 36 months | ||
| Secondary | Muscle/Bone: musculoskeletal pain | Assessed with the McGill questionnaire | Baseline, 12,24, and 36 months | |
| Secondary | Cardio-vascular: Incident Hypertension | 36 months | ||
| Secondary | Brain: mental health decline | Assessed with Geriatric Depression Scale | Baseline, 12,24, and 36 months | |
| Secondary | Brain: Incident Depression | 36 months | ||
| Secondary | Brain/Muscle: Dual tasking gait variability | Subset of 250 participants | Baseline, 12, 24 and 36 months | |
| Secondary | Immunity: Rate of upper respiratory infections / rate of flu-like illness | Assessed with infection protocol every 3 months | 36 months | |
| Secondary | Immunity: Incident severe infections that lead to hospital admission | 36 months | ||
| Secondary | Cartilage/Bone: Severity of knee pain in participants with symptomatic knee osteoarthritis | Assessed with the KOOS questionnaire. Knee OA assessment with modified ACR criteria. | Baseline, 12, 24 and 36 months | |
| Secondary | Cartilage/Bone: Rate of knee buckling | Questionnaire-based. | Baseline, 12,24,36 months | |
| Secondary | Cartilage/Bone: NSAID use / number of joints with pain | Assessed by questionnaire and homunculus figure | Baseline, 12, 24, 36 months | |
| Secondary | Dental: Decline in oral health | Assessed with questionnaire. | Baseline, 12,24 and 36 months | |
| Secondary | Dental: Tooth loss | Assessed by tooth count at every clinical visit | 36 months | |
| Secondary | Gastro-Intestinal: rate of GI symptoms | Assessed with ROME III questionnaire. | Baseline, 12, 24 and 36 months | |
| Secondary | 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) | Baseline, 12,24,36 months | |
| Secondary | Glucose-Metabolic: Body composition | Subset of 1502 participants with DXA measurements | Baseline, 12, 24, 36 months | |
| Secondary | Kidney: Decline in kidney function | Blood creatinine levels and estimated glomerular filtration rate | Baseline, 12, 24, and 36 months | |
| Secondary | Global Health: Quality of life | Assessed with questionnaire (EuroQuol). | Every 6 months | |
| Secondary | Global Health: Incident disability regarding activities of daily living | Assessed with HAQ-PROMIS questionnaire | Baseline, 12, 24 and 36 months | |
| Secondary | Global Health: Incident nursing home admission | 36 months | ||
| Secondary | Global Health: Mortality | 36 months |