Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Temporarily halted
Participants planned
180
Countries
1
Sites
3
Patients with acquired partial/total vision impairments
This clinical trial aims to investigate the potential underlying mechanisms of action of zolpidem in three groups of patients with disorders of consciousness (DoC), neurotypical volunteers representing the general population, and patients with partial/total acquired vision impairments as certain proportion of people in…
Key facts
- Sponsor
- Universite De Liege, CHU De Liege
- Participant type
- Patients, Healthy volunteers
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Nervous System Diseases [C10], Phenomena and Processes [G] - Physiological processes [G07]
- Trial duration
- 11 Feb 2025 → ongoing
- Decision date (initial)
- 2025-01-23
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Efficacy, Therapy
This clinical trial aims to investigate the potential underlying mechanisms of action of zolpidem in three groups of patients with disorders of consciousness (DoC), neurotypical volunteers representing the general population, and patients with partial/total acquired vision impairments as certain proportion of people in all these groups respond paradoxically to zolpidem. Paradoxical responses to zolpidem lead to recovery of consciousness in DoC patients and temporary recovery of vision in patients with vision impairments. Neurotypical volunteers with paradoxical responses also show inability to fall asleep, higher levels of concentration, increased agitation, etc. Therefore, the findings of this study could contribute to a better understanding of the mechanisms of action of zolpidem in paradoxical responders vs. non-paradoxical responders to zolpidem and can lead to improved personalised patient care.
Conditions and MedDRA coding
Patients with acquired partial/total vision impairments
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Mechanisms of Action of Paradoxical Responses to Zolpidem: A Multimodal Study We will examine neurophysiological and behavioural correlates of paradoxical responses to zolpidem within a two-day randomised placebo-controlled clinical trial. Paradoxical responders and non-paradoxical responders will be recruited within three groups of patients with disorders of consciousness, neurotypical volunteers representing the general population, and patients with partial/total acquired vision impairments. Using a cross-over placebo/treatment design, all the participants will receive one dose of zolpidem (10mg) and one dose of placebo (Mannitol 10%; orally or via gastric tube). Behavioral scales will be used to evaluate the level of arousal and awareness before and after the zolpidem in all the groups. Electroencephalography will be recorded from 15 minutes before and up to one hour after the IMP/placebo administration. Cognitive tests will be completed by neurotypical volunteers and patients with vision impairments after IMP/placebo administration. Ophthalmological tests will be performed in patients with vision impairments after IMP/placebo administration. There will be two different sessions (zolpidem, placebo) one week apart to avoid carry-over effects. These sessions should last approximately 4h and will be done at the same time of the day to account for circadian modulation.
|
2 | Double | [{"id":104381,"code":1,"name":"Subject"},{"id":104383,"code":4,"name":"Analyst"},{"id":104382,"code":5,"name":"Carer"},{"id":104380,"code":2,"name":"Investigator"}] | Neurotypical volunteers representing the general population: Paradoxical and non-paradoxical responders to zolpidem Patients with Disorders of Consciousness: Patients with an Unresponsive Wakefulness Syndrome (UWS), patients in a Minimally Conscious State (MCS), and patients emerging from MCS (EMCS) who respond paradoxically (showing signs of consciousness recovery) and non-paradoxically (showing expected somnolence effects) to zolpidem. Patients with vision impairments: Patients with partial/total acquired vision impairments responding paradoxically (showing signs of vision recovery) and non-paradoxically (showing expected somnolence effects) to zolpidem |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- DoC patients: >18 years old; >28 days post-injury; diagnosis of UWS, MCS-, MCS+ or EMCS according to international guidelines and behavioural assessments with CRS-R; stable vital parameters; no neurological deficits prior to brain injury; signed consent form (by the patient if capable of giving informed consent or by the patient’s legal guardian). All patients will be observed at least one week prior to intervention to establish their baseline clinical profile.
- Neurotypical volunteers: ≥18 years of age; no psychiatric/neurological disorders at the time of inclusion; a good state of health; negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) for WOCBP* within 24 hours prior to the start of the CT; WOCBP and male participants who are sexually active with WOCBP must agree to follow method(s) of contraception from 48 hours before the start of the trial until 24 hours (>4 half-life of zolpidem) after the termination of the trial; signed consent form.
- Patients with vision impairments: ≥18 years of age; acquired total/partial vision impairments documented following relevant testing by a neuro-ophthalmologist; no psychiatric/neurological disorders at the time of inclusion; negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) for WOCBP within 24 hours prior to the start of the CT; WOCBP and male participants who are sexually active with WOCBP must agree to follow method(s) of contraception from 48 hours before the start of the trial until 24 hours (>4 half-life of zolpidem) after the termination of the trial; signed consent form.
Exclusion criteria 3
- DoC patients: Use of ketoconazole, fluvoxamine, and/or ciprofloxacine in the last 7 days or 4 half-lives of the drug before the initiation of the experiment; use of zolpidem in the last 24 hours before the start of any phase of the study; contraindications to EEG (e.g., skin sensitivity).
- Neurotypical volunteers: Use of ketoconazole, fluvoxamine, and/or ciprofloxacine in the last 7 days or 4 half-lives of the drug before the initiation of the experiment; use of zolpidem in the last 24 hours before the start of any phase of the study; contraindications to EEG (e.g., skin sensitivity); breastfeeding (women), pregnancy (women).
- Patients with vision impairments: Use of ketoconazole, fluvoxamine, and/or ciprofloxacine in the last 7 days or 4 half-lives of the drug before the initiation of the experiment; use of zolpidem in the last 24 hours before the start of any phase of the study; contraindications to EEG (e.g., skin sensitivity); breastfeeding (women), pregnancy (women).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- DoC patients: Consciousness level (Coma Recovery Scale-Revised – CRS-R); Neural complexity (high density electroencephalography – hdEEG); Phenomenological experiences (Free recall/interview, if the patient recovers functional communication after IMP/placebo administration)
- Neurotypical volunteers: Alertness/sleepiness level (Karolinska Sleepiness Scale – KSS); Cognitive performance (Standardised neuropsychological tests); Neural complexity (high density electroencephalography – hdEEG); Phenomenological experiences (Free recall/interview)
- Patients with vision impairments: Alertness/sleepiness level (Karolinska Sleepiness Scale – KSS); Cognitive performance (Standardised neuropsychological tests); Neural complexity (high density electroencephalography – hdEEG); Phenomenological experiences (Free recall/interview); Visual functions (ophthalmological testing by a neuro-ophthalmologist)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Zolpidem Viatris 10 mg comprimés pelliculés
PRD10503685 · Product
- Active substance
- Zolpidem Tartrate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N05CF02 — ZOLPIDEM
- Marketing authorisation
- BE253617
- MA holder
- VIATRIS GX
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
SUB03087MIG · Substance
- Active substance
- Mannitol
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universite De Liege
- Sponsor organisation
- Universite De Liege
- Address
- Avenue De L'hopital 3
- City
- Liege
- Postcode
- 4000
- Country
- Belgium
Scientific contact point
- Organisation
- Universite De Liege
- Contact name
- Pr. Vincent Bonhomme
Public contact point
- Organisation
- Universite De Liege
- Contact name
- Pr. Vincent Bonhomme
CHU De Liege
- Sponsor organisation
- CHU De Liege
- Address
- Avenue De L'hopital 1
- City
- Liege
- Postcode
- 4000
- Country
- Belgium
Scientific contact point
- Organisation
- CHU De Liege
- Contact name
- Pr. Vincent Bonhomme
Public contact point
- Organisation
- CHU De Liege
- Contact name
- Pr. Vincent Bonhomme
Sponsor responsibilities
- Article 77 compliance
- Universite De Liege
- Contact point sponsor
- Universite De Liege
- Article 77 implementation
- Universite De Liege
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Temporarily halted | 180 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2025-02-11 | 2025-02-11 | 2026-03-23 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-124683
- Halt date
- 2026-03-23
- Planned restart
- 2026-05-01
- Member states concerned
- Belgium
- Publication date
- 2026-03-23
- Reason
- Investigator/Site related, Study management related
- Explanation
- A substantial amendment will be submitted in the coming days, so the recruitment is paused and it will be restarted once the amendment is approved.
- Follow-up measures
- The amendment is not safety-related and there is no long-term follow-up phase in the protocol that can be impacted by this halt.
- Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol2023-507404-31-03 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_fr | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Zolpidem | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE 2023-507404-31-03_de | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE 2023-507404-31-03_fr | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis BE 2023-507404-31-03_nl | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Belgium | Acceptable 2025-01-23
|
2025-01-23 |