Clinical trial NCT03454646: Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
Official title: Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Alzheimer Disease
Cholinesterase Inhibitors
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2018-03-06
Enrollment: 1205
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Non Inclusion Criteria:

* 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

Primary outcomes:
measure: The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.
timeFrame: at 30 months after patient's inclusion
Secondary outcomes:
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at inclusion
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at 6 months
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at 12 months
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at 18 months
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at 24 months
measure: BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
timeFrame: at 30 months
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at inclusion
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at 6 months
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at 12 months
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at 18 months
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at 24 months
measure: Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
timeFrame: at 30 months
measure: Institutionalization with date of entry
timeFrame: at inclusion
measure: Institutionalization with date of entry
timeFrame: at 6 months
measure: Institutionalization with date of entry
timeFrame: at 12 months
measure: Institutionalization with date of entry
timeFrame: at 18 months
measure: Institutionalization with date of entry
timeFrame: at 24 months
measure: Institutionalization with date of entry
timeFrame: at 30 months
measure: Death and date of death
timeFrame: at inclusion
measure: Death and date of death
timeFrame: at 6 months
measure: Death and date of death
timeFrame: at 12 months
measure: Death and date of death
timeFrame: at 18 months
measure: Death and date of death
timeFrame: at 24 months
measure: Death and date of death
timeFrame: at 30 months
measure: the ADL scale
timeFrame: at inclusion
measure: the ADL scale
timeFrame: at 6 months
measure: the ADL scale
timeFrame: at 12 months
measure: the ADL scale
timeFrame: at 18 months
measure: the ADL scale
timeFrame: at 24 months
measure: the ADL scale
timeFrame: at 30 months
measure: the MMSE score
timeFrame: at inclusion
measure: the MMSE score
timeFrame: at 6 months
measure: the MMSE score
timeFrame: at 12 months
measure: the MMSE score
timeFrame: at 18 months
measure: the MMSE score
timeFrame: at 24 months
measure: the MMSE score
timeFrame: at 30 months
measure: the number of hospitalizations
timeFrame: at inclusion
measure: the number of hospitalizations
timeFrame: at 6 months
measure: the number of hospitalizations
timeFrame: at 12 months
measure: the number of hospitalizations
timeFrame: at 18 months
measure: the number of hospitalizations
timeFrame: at 24 months
measure: the number of hospitalizations
timeFrame: at 30 months
measure: Pharmacologie treatments consumed by the patient
timeFrame: at inclusion
measure: Pharmacologie treatments consumed by the patient
timeFrame: at 6 months
measure: Pharmacologie treatments consumed by the patient
timeFrame: at 12 months
measure: Pharmacologie treatments consumed by the patient
timeFrame: at 18 months
measure: Pharmacologie treatments consumed by the patient
timeFrame: at 24 months
measure: Pharmacologie treatments consumed by the patient
timeFrame: at 30 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens Centre Mémoire Ressources Recherche
city: Angers
country: France
facility: CHU d'Angers Centre Mémoire Ressources Recherche
city: Bastia
country: France
facility: CHU de Bastia Centre Mémoire Ressources Recherche
city: Besançon
country: France
facility: CHU de Besançon Centre Mémoire Ressources Recherche
city: Bordeaux
country: France
facility: CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -
city: Brest
country: France
facility: CHRU Cavale Blanche Service de Gériatrie
city: Bron
country: France
facility: Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer
city: Caen
country: France
facility: CHU Côte de Nacre Service de neurologie et CMRR
city: Clermont-Ferrand
country: France
facility: CHU de Clermont Ferrand Centre Mémoire Ressources Recherche
city: Colmar
country: France
facility: Hôpital Pasteur Service de Neurologie
city: Dijon
country: France
facility: CHU de Dijon- CMRR
city: Grenoble
country: France
facility: Chu de Grenoble CMRR, Neurologie
city: Lille
country: France
facility: Hôpital Roger Salengro CMRR
city: Limoges
country: France
facility: CHU Limoges Service de neurologie et CMRR
city: Marseille
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU Montpellier Hôpital Gui de Chauliac CMRR
city: Nantes
country: France
facility: CHU de Nantes Clinique Neurologique Hôpital GR Laennec
city: Nice
country: France
facility: Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche
city: Paris
country: France
facility: APHP Hôpital Broca
city: Paris
country: France
facility: Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte
city: Paris
country: France
facility: APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR
city: Poitiers
country: France
facility: CHU La Milétrie Pôle de Gériatrie
city: Reims
country: France
facility: CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie
city: Rouen
country: France
facility: CHU de Rouen Hôpital Charles Nicolle Service Neurologie
city: Saint-Étienne
country: France
facility: Chu de Saint-Etienne, CMRR
city: Strasbourg
country: France
facility: Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR
city: Toulouse
country: France
facility: Centre de Recherche Clinique du Gérontopôle Cité de la Santé
city: Tours
country: France
facility: CHRU de Bretonneau Unité de gérontopsychiatrie
city: Vandoeuvre les nancy
country: France
facility: CHU Nancy Service de Gériatrie-CMRR
city: Villeurbanne
country: France
facility: Hospice Civil de Lyon Hôpital des Charpennes
Study officials:
References: