Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
- Conditions
- Cholinesterase InhibitorsAlzheimer Disease
- Interventions
- Drug: cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)
- Registration Number
- NCT03454646
- Lead Sponsor
- University Hospital, Bordeaux
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1205
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group randomized for continuing treatment cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine) 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.
- Primary Outcome Measures
Name Time Method The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization. at 30 months after patient's inclusion 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.
- Secondary Outcome Measures
Name Time Method BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17]. at 30 months Each of the components of the combined primary outcome, as defined above, analyzed separately As previously demonstrated, bathing and dressing are the first ADL losses, also defined by Katz et al. as the thresholds of disability \[17\] \[18\]. A total limitation in bathing and dressing will be considered (each item is coded from 0 - no limitation, to 2 - total limitation).
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 30 months 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.Institutionalization with date of entry at 30 months 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 at 30 months 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.
the ADL scale at 30 months ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
1. needs help in bathing only one part of the body
2. needs help with bathing more than one part of the body or not bathed DRESSING :└-┘ /2
0 gets clothes and gets completely dressed without assistance
1 gets clothes and gets dressed without assistance, except for assistance in tying shoes 2 receives assistance in getting clothes or in getting dressed, or stays partly or completely undressed TOILETING :└-┘/2 0 toileting without assistance (may use cane, walker, or wheelchair)
1 receives assistance 2 doesn't go to room termed " toilet ". TRANSFER:└-┘/2 0 transfer without assistance (may be using cane or walker)
1. transfer with assistance
2. doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
1. need help cutting meat or buttering bread
2. needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10the MMSE score at 30 months The MMSE score will be assessed by the clinician, the psychologist or the speech therapist according to the habits of the center, using the French version of the MMSE (GRECO version)
the number of hospitalizations at 30 months The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Pharmacologie treatments consumed by the patient at 30 months All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Trial Locations
- Locations (31)
Chu de Grenoble CMRR, Neurologie
🇫🇷Grenoble, France
Hôpital Roger Salengro CMRR
🇫🇷Lille, France
CHU d'Amiens Centre Mémoire Ressources Recherche
🇫🇷Amiens, France
CHU de Dijon- CMRR
🇫🇷Dijon, France
CHU Montpellier Hôpital Gui de Chauliac CMRR
🇫🇷Montpellier, France
CHU de Besançon Centre Mémoire Ressources Recherche
🇫🇷Besançon, France
Hôpital Pasteur Service de Neurologie
🇫🇷Colmar, France
CHU d'Angers Centre Mémoire Ressources Recherche
🇫🇷Angers, France
AP-HM
🇫🇷Marseille, France
Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer
🇫🇷Bron, France
CHU de Bastia Centre Mémoire Ressources Recherche
🇫🇷Bastia, France
CHU Côte de Nacre Service de neurologie et CMRR
🇫🇷Caen, France
APHP Hôpital Broca
🇫🇷Paris, France
Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte
🇫🇷Paris, France
CHU La Milétrie Pôle de Gériatrie
🇫🇷Poitiers, France
Centre de Recherche Clinique du Gérontopôle Cité de la Santé
🇫🇷Toulouse, France
Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR
🇫🇷Strasbourg, France
CHRU de Bretonneau Unité de gérontopsychiatrie
🇫🇷Tours, France
Hospice Civil de Lyon Hôpital des Charpennes
🇫🇷Villeurbanne, France
CHRU Cavale Blanche Service de Gériatrie
🇫🇷Brest, France
CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -
🇫🇷Bordeaux, France
CHU de Clermont Ferrand Centre Mémoire Ressources Recherche
🇫🇷Clermont-Ferrand, France
CHU Limoges Service de neurologie et CMRR
🇫🇷Limoges, France
Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche
🇫🇷Nice, France
APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR
🇫🇷Paris, France
CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique
🇫🇷Reims, France
CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie
🇫🇷Rennes, France
Chu de Saint-Etienne, CMRR
🇫🇷Saint-Étienne, France
CHU Nancy Service de Gériatrie-CMRR
🇫🇷Vandoeuvre les nancy, France
CHU de Nantes Clinique Neurologique Hôpital GR Laennec
🇫🇷Nantes, France
CHU de Rouen Hôpital Charles Nicolle Service Neurologie
🇫🇷Rouen, France