Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)

NCT ID: NCT03454646

Last Updated: 2023-10-06

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

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1205 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2027-09-15

Brief Summary

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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.

Detailed Description

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Conditions

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Alzheimer Disease Cholinesterase Inhibitors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group randomized for continuing treatment

Group 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 Type EXPERIMENTAL

cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)

Intervention Type DRUG

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.

Group randomized for stopping treatment

Group 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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* New case of AD referring to a CMRR or MC.
* Diagnosis of probable or possible AD, defined according to the NINCDS-ARDRA criteria
* Mild to moderate stage, defined by a MMSE score above 15 at the time of pre-inclusion
* 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
* More severe stage of the disease, defined by a MMSE equal or below 15 at the time of inclusion
* Patients with contraindication to CI treatment
* Patients residing in an institution at the time of pré-inclusion or randomization
* Patients with a complete dependency for bathing and dressing at the time of pré-inclusion or randomization ( ADL de Katz, score 2/2 for the item "bathing" and/or "dressing")
* 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
* Pregnant or breastfeeding women

Exclusion Criteria

* 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
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CHU d'Amiens Centre Mémoire Ressources Recherche

Amiens, , France

Site Status

CHU d'Angers Centre Mémoire Ressources Recherche

Angers, , France

Site Status

CHU de Bastia Centre Mémoire Ressources Recherche

Bastia, , France

Site Status

CHU de Besançon Centre Mémoire Ressources Recherche

Besançon, , France

Site Status

CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -

Bordeaux, , France

Site Status

CHRU Cavale Blanche Service de Gériatrie

Brest, , France

Site Status

Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer

Bron, , France

Site Status

CHU Côte de Nacre Service de neurologie et CMRR

Caen, , France

Site Status

CHU de Clermont Ferrand Centre Mémoire Ressources Recherche

Clermont-Ferrand, , France

Site Status

Hôpital Pasteur Service de Neurologie

Colmar, , France

Site Status

CHU de Dijon- CMRR

Dijon, , France

Site Status

Chu de Grenoble CMRR, Neurologie

Grenoble, , France

Site Status

Hôpital Roger Salengro CMRR

Lille, , France

Site Status

CHU Limoges Service de neurologie et CMRR

Limoges, , France

Site Status

AP-HM

Marseille, , France

Site Status

CHU Montpellier Hôpital Gui de Chauliac CMRR

Montpellier, , France

Site Status

CHU de Nantes Clinique Neurologique Hôpital GR Laennec

Nantes, , France

Site Status

Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche

Nice, , France

Site Status

APHP Hôpital Broca

Paris, , France

Site Status

Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte

Paris, , France

Site Status

APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR

Paris, , France

Site Status

CHU La Milétrie Pôle de Gériatrie

Poitiers, , France

Site Status

CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique

Reims, , France

Site Status

CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie

Rennes, , France

Site Status

CHU de Rouen Hôpital Charles Nicolle Service Neurologie

Rouen, , France

Site Status

Chu de Saint-Etienne, CMRR

Saint-Etienne, , France

Site Status

Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR

Strasbourg, , France

Site Status

Centre de Recherche Clinique du Gérontopôle Cité de la Santé

Toulouse, , France

Site Status

CHRU de Bretonneau Unité de gérontopsychiatrie

Tours, , France

Site Status

CHU Nancy Service de Gériatrie-CMRR

Vandœuvre-lès-Nancy, , France

Site Status

Hospice Civil de Lyon Hôpital des Charpennes

Villeurbanne, , France

Site Status

Countries

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France

Central Contacts

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Jean-François DARTIGUES, M.D., Ph.D

Role: CONTACT

05 57 82 01 16

François TISON, M.D., Ph.D

Role: CONTACT

05 57 82 12 54

Facility Contacts

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Agnès DEVENDEVILLE

Role: primary

03.22.66.82.40

Georges RETTALI

Role: primary

04.95.59.18.32

Jean-François DARTIGUES

Role: primary

Hélène MOLLION

Role: primary

04.72.35.71.79

Yannick BEJOT

Role: primary

03.80.29.58.03

Olivier MOREAUD

Role: primary

04 76 76 57 90

Leslie CARTZ-PIVER

Role: primary

05.55.43.12.15

Audrey GABOREAU DE LOUSTAL

Role: primary

04.67.33.60.29

Claire BOUTOLEAU

Role: primary

02.40.16.54.22

Renaud David

Role: primary

04.92.03.47.70

Olivier HANON

Role: primary

01.44.08.35.03

Stéphane EPELBAUM

Role: primary

01.42.16.75.22

Claire PAQUET

Role: primary

01.40.05.49.54

Marc PACCALIN

Role: primary

05.49.44.44.27

Jean-Luc NOVELLA

Role: primary

03.26.78.44.10

Serge BELLIARD

Role: primary

02.99.87.30.26

David Wallon

Role: primary

06.08.97.29.59

Isabelle ROUCH

Role: primary

04.77.12.73.98

Frédéric BLANC

Role: primary

03.88.12.86.38

Thomas DESMIDT

Role: primary

06.68.07.97.06

Thérèse RIVASSEAU JONVAUX

Role: primary

03.83.15.35.71

Pierre KROLAK SALMON

Role: primary

04.72.43.20.50

Other Identifiers

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CHUBX 2016/27

Identifier Type: -

Identifier Source: org_study_id

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