CIRAANO: Multimodal exploration of theater actors, memory athletes, and patients with various memory pathologies: evaluation of mnesic strategies and their cerebral substrates, and contribution to the treatment of memory pathologies.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut National De La Sante Et De La Recherche Medicale

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Decision date (initial)

2026-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

[Part 2] to evaluate, in different categories of patients with memory disorders of various origins, the preservation or alteration of memory-related brain networks, associated with different types of memory strategies identified in memory experts.

Secondary objectives 6

1. [Part 1 - Objective 1] to assess the feasibility of this trial
2. [Part 1 - Objective 2] to Assess the acceptability of the procedures by participants included in Part 1
3. [Part 2 - Objective 2] To identify the specific characteristics of theatre actors and memory athletes compared to controls, in terms of brain, cognitive, biological, and psycho-affective measures, as well as lifestyle factors, sleep, and alcohol consumption
4. [Part 2 - Objective 3] To identify the specific characteristics of various patient groups with memory disorders of different etiologies, compared to controls, theatre actors, and memory athletes, in terms of brain, cognitive, biological, and psycho-affective measures, lifestyle factors, sleep, and alcohol consumption, as well as inter-individual differences (e.g., related to sex, age, presence of risk factors, etc.)
5. [Part 2 - Objective 4] To explore the relationships between brain, biological, cognitive, psycho-affective measures, and lifestyle factors (including sleep and alcohol consumption) across the different groups (controls, actors, memory athletes, and patients), in order to deepen understanding of underlying pathophysiological mechanisms
6. [Part 2 - Objective 5] To identify the mechanisms driving the topography of brain pathology and the factors influencing its propagation over 10 to 20 years, in both controls and patients, with the aim of predicting disease progression using an artificial intelligence model

Conditions and MedDRA coding

Semantic Variant Primary Progressive Aphasia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 42

1. [all participants] Minimum education level of 7 years (at least equivalent to the French Certificat d’Études Primaires (CEP))
2. [all participants] Native French speaker and educated in French
3. [all participants] Affiliated with a French social security scheme or beneficiary of such a scheme
4. [all participants] Willingness to undergo several days of assessments
5. [all participants] Adherence to lifestyle considerations
6. [all participants] Signed informed consent to participate in the study
7. [ACT] Aged 18 or older
8. [ACT] Must have performed in at least one theatre play in the last three years
9. [ACT] Must be or have been a professional actor, either freelance or permanent (e.g., in a theatre company or at the Comédie-Française) for at least 5 years
10. [HC] Aged 18 or older
11. [HC] Neuropsychological performance within the normal range for age and education level on all inclusion battery tests (±1.65 standard deviation)
12. [HC] Be considered capable of complying with the protocol according to the investigator's judgment
13. [ATHL] Aged 18 or older
14. [ATHL] Must have participated in a memory competition—international, European, or national level
15. [ATHL] Be considered capable of complying with the protocol according to the investigator's judgment
16. [SCD] Aged 60 or older
17. [SCD] Recruited from memory clinics
18. [SCD] Must meet recognized criteria for subjective cognitive decline in the context of the preclinical stage of Alzheimer’s disease
19. [MCI-AD] Aged 60 or older
20. [MCI-AD] Recruited from memory clinics
21. [MCI-AD] Must meet current recognized clinical criteria for mild cognitive impairment due to Alzheimer’s disease
22. [D-AD] Aged 60 years or older
23. [D-AD] Recruited from memory clinics
24. [D-AD] Meeting current and recognized clinical criteria for major neurocognitive disorder due to probable Alzheimer’s disease
25. [LBD] Aged 60 years or older
26. [LBD] Recruited from memory clinics
27. [LBD] Meeting current and recognized clinical criteria for probable Lewy body dementia or probable prodromal Lewy body dementia (mild cognitive impairment with Lewy bodies)
28. [svPPA] Aged 50 years or older
29. [svPPA] Recruited from memory clinics
30. [svPPA] Meeting current and recognized clinical criteria for semantic dementia
31. [AUD] Aged 18 years or older
32. [AUD] Recruited from an addiction treatment service
33. [AUD] Undergoing treatment primarily for an alcohol use disorder at the time of inclusion
34. [AUD] Detoxified, with withdrawal symptoms resolved (Cushman score <3, Cushman et al., 1985) and benzodiazepines discontinued at the time of inclusion
35. [AUD] Abstinent from all psychoactive substances (except tobacco and prescribed medication) at the time of inclusion
36. [AMN] Aged 18 years or older
37. [AMN] Recruited from hospital services or residential facilities housing patients with non-degenerative amnesic syndromes
38. [AMN] Presenting with major cognitive impairment : Characterized primarily by severe episodic memory deficits (anterograde amnesia), possibly associated with retrograde amnesia and/or other impairments ; Leading to significant impacts on daily functioning and reduced autonomy ; Persistent and stable over time
39. [NARCO] Aged 18 years or older
40. [NARCO] - Diagnosed with type 1 narcolepsy according to the 3rd edition of the International Classification of Sleep Disorders (ICSD-3), which includes daytime sleepiness persisting for more than 3 months, and either : Presence of cataplexy, mean sleep latency <8 minutes on the Multiple Sleep Latency Test (MSLT), and at least two REM sleep onsets (on MSLT and/or overnight polysomnography) ; Or cerebrospinal fluid hypocretin level <110 pg/mL.
41. [Informant] Aged 18 years or older
42. [Informant] Spending at least one day per week with a relative included in one of the patient groups

Exclusion criteria 27

1. [all participants except informants] Pregnant or breastfeeding women
2. [all participants except informants] Chronic use of medications that affect cognition and/or may interfere with cognitive or imaging assessments (including non-tricyclic antidepressants, anticonvulsants such as lamotrigine, pregabalin, levetiracetam ; atypical antipsychotics; short-/intermediate-acting benzodiazepines such as alprazolam, lorazepam, oxazepam, temazepam; and sedative antihistamines), if doses were not stabilized within the 6 weeks prior to inclusion (except for changes due to withdrawal treatment in AUD patients)
3. [all participants except informants] Current use of long-acting benzodiazepines, typical antipsychotics, tricyclic antidepressants, or first-generation antihistamines at the time of inclusion (unless related to withdrawal treatment in AUD patients), with discontinuation of such medication less than 3 months prior to inclusion
4. [all participants except informants] Physical, behavioral, or geographical limitations preventing participation in the study
5. [all participants except informants] Refusal to cooperate during assessments
6. [HC] Current or recent (within the last 5 years) theater practice
7. [HC] Presence of depressive symptoms (MADRS score > 19, threshold for moderate depression)
8. [ACT & ATHL] Presence of depressive symptoms (MADRS score > 19, threshold for moderate depression)
9. [ACT & ATHL] Use of Alzheimer’s disease medications (including but not limited to donepezil, rivastigmine, galantamine, and memantine) at non-stabilized doses within 8 weeks prior to the inclusion visit
10. [all participants except informants] Presence of contraindications to MRI (e.g., claustrophobia, ferromagnetic objects in the body) or to Amyvid® and Tauvid® PET scans.
11. [SCD] Presence of depressive symptoms (MADRS score > 34, threshold for severe depression)
12. [MCI-AD] Presence of depressive symptoms (MADRS score > 34, threshold for severe depression)
13. [MCI-AD] Use of Alzheimer’s disease medications (including but not limited to donepezil, rivastigmine, galantamine, and memantine) at non-stabilized doses within 8 weeks prior to the inclusion visit
14. [D-AD, LBD & svPPA] Presence of depressive symptoms (MADRS score > 34, threshold for severe depression)
15. [D-AD, LBD & svPPA] Absence of a caregiver or informant (i.e., a trusted person or relative who will be present from inclusion through the assessments, for patients with major cognitive impairment)
16. [D-AD, LBD & svPPA] Use of Alzheimer’s disease medications (including but not limited to donepezil, rivastigmine, galantamine, and memantine) and/or L-DOPA for LBD patients, at non-stabilized doses within 8 weeks prior to the inclusion visit
17. [D-AD, LBD & svPPA] Inability to understand instructions
18. [AUD & AMN] Presence of depressive symptoms (MADRS score > 34, threshold for severe depression)
19. [AUD & AMN] Evidence suggesting a probable neurodegenerative disorder (e.g., impairment in instrumental cognitive functions)
20. [all participants except informants] Known hypersensitivity to Amyvid® or Tauvid®
21. [NARCO] Presence of depressive symptoms (MADRS score > 34, threshold for severe depression)
22. [all participants except informants] Participation in a clinical study involving exposure to ionizing radiation within the year prior to inclusion
23. [all participants except informants] Current participation in a clinical trial and/or other research involving human participants (RIPH) if it includes imaging examinations using radiotracers
24. [all participants except informants] History of neurological or neurosurgical conditions that could significantly affect cognitive function and/or neuroimaging (e.g., head trauma with loss of consciousness >30 minutes, stroke, multiple sclerosis, insulin coma)
25. [all participants except informants] Schizophrenia, psychotic disorders, or bipolar disorders (according to DSM-5 criteria)
26. [all participants except informants] Having a score suggesting an alcohol dependence (>9) on the FACE questionnaire (except for AUD patients)
27. [all participants except informants] Presence of untreated chronic or acute illnesses (respiratory, cardiovascular, gastrointestinal, renal, metabolic, hematologic, endocrine, or infectious)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. [Part 2 - Objective 1] Volume measurements (from T1 MRI) and perfusion measurements (from early-phase Amyvid® PET) in the 4 brain networks in each patient group and in controls

Secondary endpoints 29

1. [Part 1 - Objective 1] Number of participants having successfully completed all examinations necessary for the evaluation of the main judgement criterion of CIRAANO
2. [Part 1 - Objective 2] Score obtained on the acceptability scale
3. Behavioral data collected using the various questionnaires
4. Raw scores from neuropsychological tests
5. Scores from the directed forgetting task (number of “To Remember” and “To Forget” words identified as new or previously seen)
6. Composite scores by cognitive function and domain (lifestyle factors, sleep, psycho-affective or subjective evaluation) assessed by neuropsychological tests and questionnaires. Composite scores correspond to an average of standardized z-scores, calculated from the raw scores collected in the control group for the corresponding function (scores presenting a normal distribution and without floor/ceiling effects)
7. Ranking position in the national memory sports classification (for the memory athlete group)
8. Theater experience and practice, in terms of time and number of plays learned (for the actor group)
9. Gray matter volume measured in each voxel of the brain
10. Volume of the hippocampus and hippocampal subfields
11. Volume of the thalamus and thalamic subregions
12. Mean intensity value of the locus coeruleus
13. Cerebral perfusion measured in each voxel of the brain
14. Fractional anisotropy, mean diffusivity, and mean kurtosis in each voxel of the brain
15. Number, size, and location of white matter lesions
16. Functional brain connectivity
17. Beta-amyloid burden (from the radiopharmaceutical Amyvid®) measured in each voxel of the brain and overall mean in gray matter
18. Burden of neurofibrillary tangles or abnormally phosphorylated Tau protein (from the radiopharmaceutical Tauvid®) measured in each voxel of the brain and overall mean in the temporal region
19. Brain activity measured by fMRI specifically associated with recall, encoding, and learning from the text learning task (compared to activity measured during control tasks of reading and verbal articulation)
20. Data collected during EEG recording associated with the passive listening task of auditory stimuli
21. Spontaneous oscillatory activity (EEG) in a resting state
22. Subjective sleep measures collected through sleep questionnaires
23. Data collected through actigraphy
24. Data collected through polysomnographic recordings
25. Data collected through the SomnoArt® device
26. Blood measures
27. Anthropometric and physical measures (from the medical interview, ECG analysis from polysomnographic recording during a wakeful state)
28. Measurement of liver fibrosis using Fibroscan®
29. Scores from questionnaires and information about the relative (age, type of relationship with the participant, frequency of meetings, number of years of relationship) provided by the accompanying persons/informants depending on the participant’s group

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut National De La Sante Et De La Recherche Medicale

Sponsor organisation

Institut National De La Sante Et De La Recherche Medicale

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

scientific manager

Public contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

scientific manager

Third parties 2

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications