Alzheimer DiseasePhase 4NCT03454646
Comparison of Therapeutic Strategies With Cholinesterase Inhibitors (SOS TRIAL)
A Phase 4 study testing cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine) in people with Alzheimer Disease and Cholinesterase Inhibitors, run by University Hospital, Bordeaux at 31 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease, Cholinesterase Inhibitors
- What is being tested?
- cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,205 participants
- Where
- 31 sitesFrance
- Study dates
- 1 Jun 2024to 15 Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 21Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
31 sites in 1 country. Contact the study team or a site near you to ask about taking part.
31 sites in 1 country
France31 sites
CHU d'Amiens Centre Mémoire Ressources Recherche
Amiens, 80054
Agnès DEVENDEVILLE, 03.22.66.82.40, devendeville.agnes@chu-amiens.fr
CHU d'Angers Centre Mémoire Ressources Recherche
Angers, 49933
CHU de Bastia Centre Mémoire Ressources Recherche
Bastia, 20604
Georges RETTALI, 04.95.59.18.32, georges.retali@ch-bastia.fr
CHU de Besançon Centre Mémoire Ressources Recherche
Besançon, 25030
CHU de Bordeaux - Service de Neurologie - Centre Mémoire Ressources Recherche -
Bordeaux, 33076
Jean-François DARTIGUES, 0557820116, jean-françois.dartigues@u-bordeaux.fr
CHRU Cavale Blanche Service de Gériatrie
Brest, 29200
Service de Neuropsychologie Hôpital Neurologique Pierre Wertheimer
Bron, 69677
Hélène MOLLION, 04.72.35.71.79, helene.mollion@chu-lyon.fr
CHU Côte de Nacre Service de neurologie et CMRR
Caen, 14033
CHU de Clermont Ferrand Centre Mémoire Ressources Recherche
Clermont-Ferrand, 63000
Hôpital Pasteur Service de Neurologie
Colmar, 68000
CHU de Dijon- CMRR
Dijon, 21679
Yannick BEJOT, 03.80.29.58.03, yannick.bejot@chu-dijon.fr
Chu de Grenoble CMRR, Neurologie
Grenoble, 38043
Olivier MOREAUD, 04 76 76 57 90, omoreaud@chu-grenoble.fr
Hôpital Roger Salengro CMRR
Lille, 59037
CHU Limoges Service de neurologie et CMRR
Limoges, 87000
Leslie CARTZ-PIVER, 05.55.43.12.15, Lcp.coglim@gmail.com
AP-HM
Marseille
CHU Montpellier Hôpital Gui de Chauliac CMRR
Montpellier, 34295
Audrey GABOREAU DE LOUSTAL, 04.67.33.60.29, a-gabelle@chu-montpellier.fr
CHU de Nantes Clinique Neurologique Hôpital GR Laennec
Nantes, 44093
Claire BOUTOLEAU, 02.40.16.54.22, claire.boutoleaubretonniere@chu-nantes.fr
Institut Claude Pompidou Centre Mémoire de Ressources et de Recherche
Nice, 06100
Renaud David, 04.92.03.47.70, claire.paquet@inserm.fr
APHP Hôpital Broca
Paris, 75013
Olivier HANON, 01.44.08.35.03, olivier.hanon@brc.aphp.fr
Hôpital Universitaire de la Pitié Salpêtrière Pavillon François Lhermitte
Paris, 75013
Stéphane EPELBAUM, 01.42.16.75.22, stephane.epelbaum@psl.aphp.fr
APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal CMRR
Paris, 75475
Claire PAQUET, 01.40.05.49.54, claire.paquet@inserm.fr
CHU La Milétrie Pôle de Gériatrie
Poitiers, 86021
Marc PACCALIN, 05.49.44.44.27, m.paccalin@chu-poitiers.fr
CHU Reims Hôpital Maison Blanche Court Séjour Gériatrique
Reims, 51092
Jean-Luc NOVELLA, 03.26.78.44.10, jl.novella@chu-reims.fr
CHU de Rennes - Hôpital Pontchaillou / Service de Neurologie
Rennes, 35033
Serge BELLIARD, 02.99.87.30.26, serge.belliard@chu-rennes.fr
CHU de Rouen Hôpital Charles Nicolle Service Neurologie
Rouen, 76031
David Wallon, 06.08.97.29.59, david.wallon@chu-rouen.fr
Chu de Saint-Etienne, CMRR
Saint-Etienne, 42055
Isabelle ROUCH, 04.77.12.73.98, isabelle.rouch@chu-st-etienne.fr
Chu de Strasbourg Hôpital Ka Robertsau Pôle de Gériatrie - CMRR
Strasbourg, 67200
Frédéric BLANC, 03.88.12.86.38, frederic.blanc@chru-strasbourg.fr
Centre de Recherche Clinique du Gérontopôle Cité de la Santé
Toulouse
CHRU de Bretonneau Unité de gérontopsychiatrie
Tours, 37000
Thomas DESMIDT, 06.68.07.97.06, t.desmidt@chu-tours.fr
CHU Nancy Service de Gériatrie-CMRR
Vandœuvre-lès-Nancy, 54511
Thérèse RIVASSEAU JONVAUX, 03.83.15.35.71, t.jonveaux@chu-nancy.fr
Hospice Civil de Lyon Hôpital des Charpennes
Villeurbanne, 69100
Pierre KROLAK SALMON, 04.72.43.20.50, pierre.krolak-salmon@chu-lyon.fr
About this study
Official title: Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial
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.
- Conditions
- Alzheimer Disease, Cholinesterase Inhibitors
- Being tested
- cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine)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.
| Study group | Role | What they receive |
|---|---|---|
| Group randomized for continuing treatment | Experimental | 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. Receives: Drug: cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine) |
| Group randomized for stopping treatment | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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].
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).
Measured: at inclusion
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
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).
Measured: at 6 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
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).
Measured: at 12 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
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).
Measured: at 18 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
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).
Measured: at 24 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
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).
Measured: at 30 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at inclusion
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at 6 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at 12 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at 18 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at 24 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
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.
Measured: at 30 months
Institutionalization with date of entry
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.
Measured: at inclusion
Institutionalization with date of entry
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.
Measured: at 6 months
Institutionalization with date of entry
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.
Measured: at 12 months
Institutionalization with date of entry
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.
Measured: at 18 months
Institutionalization with date of entry
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.
Measured: at 24 months
Institutionalization with date of entry
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.
Measured: at 30 months
Death and date of death
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.
Measured: at inclusion
Death and date of death
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.
Measured: at 6 months
Death and date of death
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.
Measured: at 12 months
Death and date of death
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.
Measured: at 18 months
Death and date of death
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.
Measured: at 24 months
Death and date of death
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.
Measured: at 30 months
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10 If the patient has a result of 2 at bathing and or dressing he can't be included at T0.
Measured: at inclusion
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10 If the patient has a result of 2 at bathing and or dressing he can't be randomized at T6M
Measured: at 6 months
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10
Measured: at 12 months
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10
Measured: at 18 months
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10
Measured: at 24 months
the ADL scale
ADL DE KATZ BATHING :└-┘/2 0 bathes self completely
- needs help in bathing only one part of the body
- 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)
- transfer with assistance
- doesn't get out of bed. FEEDING :└-┘/2
0 feeding without help
- need help cutting meat or buttering bread
- needs total help or requires parenteral feeding. TOTAL : └-┴-┘/10
Measured: at 30 months
the MMSE score
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)
Measured: at inclusion
the MMSE score
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)
Measured: at 6 months
the MMSE score
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)
Measured: at 12 months
the MMSE score
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)
Measured: at 18 months
the MMSE score
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)
Measured: at 24 months
the MMSE score
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)
Measured: at 30 months
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at inclusion
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at 6 months
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at 12 months
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at 18 months
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at 24 months
the number of hospitalizations
The number of hospitalizations will be assessed using standardized questionnaire, with date (month/year) and duration of hospitalization;
Measured: at 30 months
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at inclusion
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at 6 months
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at 12 months
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at 18 months
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at 24 months
Pharmacologie treatments consumed by the patient
All the pharmacologie treatments consumed by the patient will be assessed, allowing to assess psychotropic drug consumption.
Measured: at 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start1 Jun 2024 (estimated)
- Primary completion27 Apr 2027 (estimated)
- Study completion15 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,205 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03454646
- Sponsor's protocol ID
- CHUBX 2016/27
- Status last verified
- Oct 2023
- First submitted
- 9 Feb 2018
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Therapeutic Strategies With Cholinesterase Inhibitors: Stop or Still (SOS) Trial
- ClinicalTrials.gov ID
- NCT03454646
- Acronym / sponsor ID
- CHUBX 2016/27
- Conditions
- Alzheimer Disease, Cholinesterase Inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,205 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 27 Apr 2027 (estimated)
- Study completion
- 15 Sep 2027 (estimated)
- First posted
- 6 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group randomized for continuing treatment | Experimental | Drug: 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. |
| Group randomized for stopping treatment | No intervention | –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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Group randomized for continuing treatment |
Primary outcome
The primary outcome is a combination of complete BADL dependency in bathing and dressing and/or institutionalization or death at 2 years after randomization.
Time frame: 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.
48 secondary outcomes
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at inclusion
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at 6 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at 12 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at 18 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at 24 months
BADL dependency will be evaluated by the clinician using the BADL scale from Katz [17].
Time frame: at 30 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at inclusion
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at 6 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at 12 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at 18 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at 24 months
Combination of complete BADL dependency in bathing and dressing and/or institutionalization or death
Time frame: at 30 months
Institutionalization with date of entry
Time frame: at inclusion
Institutionalization with date of entry
Time frame: at 6 months
Institutionalization with date of entry
Time frame: at 12 months
Institutionalization with date of entry
Time frame: at 18 months
Institutionalization with date of entry
Time frame: at 24 months
Institutionalization with date of entry
Time frame: at 30 months
Death and date of death
Time frame: at inclusion
Death and date of death
Time frame: at 6 months
Death and date of death
Time frame: at 12 months
Death and date of death
Time frame: at 18 months
Death and date of death
Time frame: at 24 months
Death and date of death
Time frame: at 30 months
the ADL scale
Time frame: at inclusion
the ADL scale
Time frame: at 6 months
the ADL scale
Time frame: at 12 months
the ADL scale
Time frame: at 18 months
the ADL scale
Time frame: at 24 months
the ADL scale
Time frame: at 30 months
the MMSE score
Time frame: at inclusion
the MMSE score
Time frame: at 6 months
the MMSE score
Time frame: at 12 months
the MMSE score
Time frame: at 18 months
the MMSE score
Time frame: at 24 months
the MMSE score
Time frame: at 30 months
the number of hospitalizations
Time frame: at inclusion
the number of hospitalizations
Time frame: at 6 months
the number of hospitalizations
Time frame: at 12 months
the number of hospitalizations
Time frame: at 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cholinesterase inhibitors (CI) (donepezil, galantamine or rivastigmine) in people with Alzheimer Disease and Cholinesterase Inhibitors, run by University Hospital, Bordeaux at 31 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-François DARTIGUES, M.D., Ph.D (05 57 82 01 16, jean-francois.dartigues@u-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: at 30 months after patient's inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.