Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)

ClinicalTrials.gov ID

NCT03454646

Lead Sponsor

University Hospital, BordeauxOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 4

Enrollment

1,205Estimated

Last Update Posted

Oct 6, 2023Actual

Start Date

Jun 1, 2024Estimated

Primary Completion Date

Apr 27, 2027Estimated

Completion Date

Sep 15, 2027Estimated

Official Title

Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial

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.

• Alzheimer Disease
• Cholinesterase Inhibitors

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

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

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 Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

University Hospital, BordeauxOTHER

georges.retali@ch-bastia.fr04.95.59.18.32

helene.mollion@chu-lyon.fr04.72.35.71.79

yannick.bejot@chu-dijon.fr03.80.29.58.03

omoreaud@chu-grenoble.fr04 76 76 57 90

Lcp.coglim@gmail.com05.55.43.12.15

a-gabelle@chu-montpellier.fr04.67.33.60.29

claire.boutoleaubretonniere@chu-nantes.fr02.40.16.54.22

claire.paquet@inserm.fr04.92.03.47.70

olivier.hanon@brc.aphp.fr01.44.08.35.03

stephane.epelbaum@psl.aphp.fr01.42.16.75.22

claire.paquet@inserm.fr01.40.05.49.54

m.paccalin@chu-poitiers.fr05.49.44.44.27

jl.novella@chu-reims.fr03.26.78.44.10

serge.belliard@chu-rennes.fr02.99.87.30.26

david.wallon@chu-rouen.fr06.08.97.29.59

isabelle.rouch@chu-st-etienne.fr04.77.12.73.98

frederic.blanc@chru-strasbourg.fr03.88.12.86.38

t.desmidt@chu-tours.fr06.68.07.97.06

t.jonveaux@chu-nancy.fr03.83.15.35.71

pierre.krolak-salmon@chu-lyon.fr04.72.43.20.50

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