Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
1 other identifier
interventional
1,205
1 country
31
Brief Summary
Cholinesterase inhibitors (CI) remain the only drugs with a recognized efficacy in mild to moderate Alzheimer's disease (AD) in spite of enormous research efforts. However, these drugs presented as "symptomatic treatment" of AD are considered as having only a weak effect on the course of AD. The reimbursement of these drugs is regularly challenged due to the lack of evidence for the impact of these drugs on milestones stages of AD evolution (survival without severe dementia, restriction in Basic Activities of Daily Living - BADL) and on major consequences in public health (hospitalization and institutionalization). The great majority of previous randomized controlled trials conducted with CI have had a too short duration and the end points were limited to cognition (ADAS Cog scale), IADL (Instrumental Activities of Daily Living) function and Global Impression of Change. New evidences from the DOMINO trial (1) conducted in UK, independently of the pharmaceutical industry, showed that the true effect of CI might be more to avoid or to delay the cognitive or functional decline in AD than to improve patients; the institutionalisation (2) was also delayed. However, this trial was conducted in patients with moderate to severe AD, and the interest of the drugs at the mild to moderate stage remains questionable. The investigators have shown that a good surrogate marker of survival without severe dementia would be an increase of ADAS Cog scale of more than six points (3). A post hoc reanalysis of the pivotal RCT with two CI showed that in mild to moderate patients, CI was associated with a 15% decrease of patients with a deterioration of ADAS-Cog of more than six points in six months. Thus at the beginning of dementia the real effect of CI might be more of delaying the cognitive and functional decline, than to improve the patients. The main objective of the SOS trial is to demonstrate that the benefit of CI at the early phase of dementia is the same as at the later phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 alzheimer-disease
Started Jun 2024
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 9, 2018
CompletedFirst Posted
Study publicly available on registry
March 6, 2018
CompletedStudy Start
First participant enrolled
June 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 27, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 15, 2027
October 6, 2023
October 1, 2023
2.9 years
February 9, 2018
October 5, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.
Institutionalization with date of entry will be assessed by specialist at each follow-up time every 6 months. For patients not coming to the memory consultation, caregiver (formal and/or informal) and/or the general practitioner will be systematically contacted to obtain the information. Death and date of death will be assessed by contacting proxy or general practitioner. In case of lack of information the birth City Hall will be contacted to assess the vital status. For dependency in bathing and dressing, although it could be considered as less objective, we choose a level of total dependency, easy to assess with very low risk of misinterpretation.
at 30 months after patient's inclusion
Secondary Outcomes (48)
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
at inclusion
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
at 6 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
at 12 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
at 18 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
at 24 months
- +43 more secondary outcomes
Study Arms (2)
Group randomized for continuing treatment
EXPERIMENTALGroup who continues the cholinesterase inhibitors (CI). The treatment is one of the CI (donepezil, galantamine or rivastigmine) with market authorization and commercialized for more than 15 years in France. The choice of the treatment will be done by the specialist according to his habits; the specialist will monitor the treatment as usual. All randomised patients will then be followed-up for two years with regular assessment of judgment criteria every 6 months.
Group randomized for stopping treatment
NO INTERVENTIONGroup who stops the CI. No placebo will be given, over 2 years All randomised patients will then be followed-up for two years with regular assessment of judgment criteria every 6 months.
Interventions
The choice of the treatment will be done by the specialist according to his habits; the specialist will monitor the treatment as usual. All the recruited patients will be treated by CI according to the recommendations of the French HAS and the clinician's habits to choose the type of CI and adjust the dosage. After a 6-month period under CI treatment, patients will be classified according to the evolution of the Mini Mental State Examination (MMSE) as "non-responders" or responders. Responders patients will continue their treatment according to the habits of the clinician. Non-responder patients will be included in the RCT, with individual randomization in two groups: one group who stops the CI, one group who continues the CI. All randomized patients will then be followed-up for two years with regular assessment of judgment criteria every 6 months.
Eligibility Criteria
You may qualify if:
- New case of AD referring to a CMRR or MC.
- Diagnosis of probable or possible AD, defined according to the NINCDS-ARDRA criteria
- Patients with indication to CI treatment
- Patients Naïve to CI treatment
- Patients aged 50 years or more
- Menopause or effective contraception (for women)
- Affiliated person or beneficiary of a social security scheme
- Patients with AD LTI (Long Term Illeness)
- Patients agree to participate, with free, informed and written consent signed by the patient and his caregiver
- Patients diagnosed with Lewy bodies disease, fronto-temporal dementia, or dementia from a cause other than Alzheimer Disease
- Patients with contraindication to CI treatment
- Patients under tutorship or curatorship, patients unable to express consent
- Patients with unstable severe general disease compromising the follow-up
- Patients without caregiver
- Patients included in another pharmacological trial
- +1 more criteria
You may not qualify if:
- CI responder patients for whom the MMSE score remained stable or became higher after 6 months of treatment
- Patients with complete dependency for bathing and dressing at the randomization visit
- Patients residing in an institution at the randomization visit
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
CHU d'Amiens Centre Mémoire Ressources Recherche
Amiens, 80054, France
CHU d'Angers Centre Mémoire Ressources Recherche
Angers, 49933, France
CHU de Bastia Centre Mémoire Ressources Recherche
Bastia, 20604, France
CHU de Besançon Centre Mémoire Ressources Recherche
Besançon, 25030, France
CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -
Bordeaux, 33076, France
CHRU Cavale Blanche Service de Gériatrie
Brest, 29200, France
Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer
Bron, 69677, France
CHU Côte de Nacre Service de neurologie et CMRR
Caen, 14033, France
CHU de Clermont Ferrand Centre Mémoire Ressources Recherche
Clermont-Ferrand, 63000, France
Hôpital Pasteur Service de Neurologie
Colmar, 68000, France
CHU de Dijon- CMRR
Dijon, 21679, France
Chu de Grenoble CMRR, Neurologie
Grenoble, 38043, France
Hôpital Roger Salengro CMRR
Lille, 59037, France
CHU Limoges Service de neurologie et CMRR
Limoges, 87000, France
AP-HM
Marseille, France
CHU Montpellier Hôpital Gui de Chauliac CMRR
Montpellier, 34295, France
CHU de Nantes Clinique Neurologique Hôpital GR Laennec
Nantes, 44093, France
Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche
Nice, 06100, France
APHP Hôpital Broca
Paris, 75013, France
Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte
Paris, 75013, France
APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR
Paris, 75475, France
CHU La Milétrie Pôle de Gériatrie
Poitiers, 86021, France
CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique
Reims, 51092, France
CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie
Rennes, 35033, France
CHU de Rouen Hôpital Charles Nicolle Service Neurologie
Rouen, 76031, France
Chu de Saint-Etienne, CMRR
Saint-Etienne, 42055, France
Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR
Strasbourg, 67200, France
Centre de Recherche Clinique du Gérontopôle Cité de la Santé
Toulouse, France
CHRU de Bretonneau Unité de gérontopsychiatrie
Tours, 37000, France
CHU Nancy Service de Gériatrie-CMRR
Vandœuvre-lès-Nancy, 54511, France
Hospice Civil de Lyon Hôpital des Charpennes
Villeurbanne, 69100, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 9, 2018
First Posted
March 6, 2018
Study Start
June 1, 2024
Primary Completion (Estimated)
April 27, 2027
Study Completion (Estimated)
September 15, 2027
Last Updated
October 6, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share