An interventional study of Intranasal Midazolam (Benzodiazepine Challenge Test) and Oral Clonazepam in Autism Spectrum Disorder and Catatonia, sponsored by Tanta University. Active, not recruiting at 1 site in Egypt. Open to participants aged 10 Years to 19 Years. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by Tanta University · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to learn if benzodiazepines and ECT can treat Catatonic features in Adolescents with Autistic spectrum disorder, it will also learn about Safety and efficacy of benzodiazepines and ECT.
the main questions it aim to answer is if adolescents with profound Autism presenting with catatonic features will show significant improvement on treatment with either benzodiazepines or ECT with no major side effects.
it is an open label pilot study whose participants diagnosed with profound autism presenting with catatonia will receive loading midazolam then maintenance clonazepam daily / ECT sets will be followed up every 2 weeks in 1st month then once / month for next 2 months, observation of symptom improvement will be tracked.
Clinical outcomes will be assessed using the Pediatric Catatonia Rating Scale as the primary outcome measure and the Aberrant Behavior Checklist as a secondary outcome measure. Participants will be followed for three months to evaluate treatment response and safety.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent impairments in social communication and interaction, along with restricted and repetitive patterns of behavior. A subgroup of individuals with ASD meets criteria for profound autism, defined by severe functional impairment requiring continuous supervision, very limited or absent language, and typically a significant intellectual disability (IQ \< 50). Adolescents with profound autism often present with severe challenging behaviors, including agitation, aggression, self-injury, and marked functional deterioration.
Catatonia is a complex neuropsychiatric syndrome characterized by a range of psychomotor disturbances such as stupor, mutism, posturing, negativism, agitation, and stereotyped movements. Increasing evidence suggests that catatonia occurs with increased frequency in adolescents and young adults with ASD, particularly those with more severe functional impairment. Catatonic symptoms in individuals with autism may be under-recognized due to overlap with baseline autistic behaviors, leading to delays in diagnosis and treatment.
This open label pilot study aims to explore the presence of catatonic features among Egyptian adolescents with profound autism and to evaluate the efficacy and safety of benzodiazepines and electroconvulsive therapy (ECT) in their management.
The study will be conducted at the Psychiatry and Neurology Center, Tanta University Hospitals, Egypt. Adolescents aged 10 to 19 years with a diagnosis of profound autism attending child and adolescent psychiatry clinics will be screened for catatonic features during the study period. Diagnosis of ASD will be confirmed according to DSM-5 criteria, supported by standardized assessment using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), along with documentation of intellectual disability using the Stanford-Binet Intelligence Scales (Fifth Edition).
All eligible participants will undergo comprehensive psychiatric evaluation, medical examination, and standardized assessments, including the Pediatric Catatonia Rating Scale (PCRS) and the Aberrant Behavior Checklist (ABC). Participants who screen positive for catatonia on the PCRS and meet criteria for the intervention phase will be offered a benzodiazepine challenge test using intranasal midazolam.
A positive benzodiazepine challenge is defined as a reduction of at least 50% in catatonic symptoms on the PCRS within 30 minutes of administration. Participants demonstrating a positive response will be treated with oral clonazepam at the lowest effective and tolerated dose and followed for three months, with assessments conducted every two weeks using the PCRS as the primary outcome measure and the ABC as a secondary outcome measure.
Participants who do not show a sufficient response to benzodiazepines will be offered treatment with electroconvulsive therapy (ECT) following caregiver consent. ECT will be administered under general anesthesia using bilateral electrode placement and brief-pulse stimulation. The acute treatment course will consist of two sessions per week for four weeks, followed by continuation treatment once weekly for up to eight weeks in participants demonstrating clinical improvement. Clinical response will be defined as a reduction of at least 50% in PCRS scores. Follow-up assessments will continue biweekly for three months.
Safety monitoring will be conducted throughout the study period, and any adverse events related to benzodiazepines or ECT will be documented. Written informed consent will be obtained from caregivers prior to participation, and all procedures will be conducted in accordance with ethical standards approved by the institutional ethics committee.
This study represents the first investigation of catatonia in adolescents with profound autism in Egypt and the Arab world and aims to contribute to improved recognition and management of this underdiagnosed but treatable condition.
1,724 studies on the registry are indexed under Autism Spectrum Disorder; 500 are open to participants now.
This study's enrollment of 30 is below the median of 52 across 1,368 interventional studies indexed under Autism Spectrum Disorder.
Browse Autism Spectrum Disorder studies →Tanta University is the lead sponsor of 1,010 studies on the registry; 321 are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Adolescents aged 10 to 19 years (defined per WHO as the second decade of life). Diagnosis of Autism Spectrum Disorder (ASD) according to criteria, with significant language impairment.
Exceeds diagnostic threshold on the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Module 1 (for minimal or no speech) OR Module 2 (for phrase speech) AND estimated IQ below 50 on the Stanford-Binet Intelligence Scales, 5th Edition.
For Intervention Group (those proceeding to benzodiazepine challenge ± ECT):
Meets all screening group inclusion criteria. Recent history of severe challenging behaviors (e.g., agitation, aggression, self-injury) to at least two trials of Applied Behavioral Analysis (ABA) AND at least one adequate trial of an antipsychotic medication approved for irritability in ASD (e.g., risperidone or aripiprazole, with sufficient dose and duration).
Screens positive for catatonic features on the Pediatric Catatonia Rating Scale (PCRS; modified Bush-Francis Catatonia Rating Scale for children and adolescents).
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adolescents aged 10-19 with profound autism and catatonic features, screened positive on the Pediatric Catatonia Rating Scale, and with recent severe challenging behaviors unresponsive to prior treatments. All participants undergo a benzodiazepine challenge test with intranasal midazolam. Responders (≥50% symptom improvement) receive oral clonazepam maintenance. Non-responders receive electroconvulsive therapy (ECT). Follow-up assessments occur every two weeks for 3 months using the Pediatric Catatonia Rating Scale (primary) and Aberrant Behavior Checklist (secondary). No control or comparator arm is included.
Drug: Intranasal Midazolam (Benzodiazepine Challenge Test) · Drug: Oral Clonazepam · Device: Electroconvulsive Therapy (ECT) · Other: Standard Assessments and Monitoring
Administered as a challenge test to all participants in the intervention group using the 5 mg/mL injectable formulation. Dose: 0.2-0.3 mg/kg (max single dose 10 mg), repeatable in 5-15 minutes up to 0.5 mg/kg (max total 10 mg). Delivered intranasally (half dose per nostril) to assess response via Pediatric Catatonia Rating Scale at 30 minutes.
Participants who show \>50% reduction in PCRS score after the midazolam challenge receive oral clonazepam drops. Treatment starts at 2 mg/day and is gradually titrated over 2 weeks up to a maximum of 6 mg/day (in 2-3 divided doses) according to clinical response and tolerability. Participants are maintained on the lowest effective and tolerated dose and followed for 3 months. Patients who fail to achieve or maintain ≥50% improvement after 1 month at maximum tolerated dose (up to 8 mg/day) are shifted to ECT.
Participants who do not respond to the benzodiazepine challenge (\>50% PCRS reduction) or who fail oral clonazepam after 1 month at maximum dose receive bilateral (bitemporal) electrode ECT under general anesthesia using a brief-pulse, computer-controlled ECT device. The initial intensive phase consists of sessions administered twice per week for 4 weeks. Participants who achieve ≥50% reduction in PCRS score proceed to a maintenance phase with sessions once per week for an additional 8 weeks (total treatment duration up to 12 weeks). Pre-ECT evaluation includes CBC, liver and renal function tests, thyroid profile, coagulation profile, ECG, and neuroimaging as clinically indicated.
All participants undergo standardized assessments including psychiatric evaluation (DSM-5), medical examination, IQ testing (Stanford-Binet 5th Edition), Social Communication Questionnaire (SCQ), ADOS-2 (Module 1 or 2), PCRS (at baseline, 30 min post-challenge, and weeks 2, 4, 8, 12), and Aberrant Behavior Checklist (ABC) at baseline and weeks 2, 4, 8, 12. Side effects are actively monitored throughout the study.
Change in Pediatric Catatonia Rating Scale (PCRS) score from baseline to week 12
Severity of catatonic symptoms as measured by the Pediatric Catatonia Rating Scale (PCRS), a modified version of the Bush-Francis Catatonia Rating Scale adapted for use in children and adolescents. The PCRS is a clinician-rated scale with up to 23 items (maximum total score = 60), assessing psychomotor disturbances including stupor, mutism, posturing, negativism, withdrawal, excitement, stereotypy, mannerisms, echolalia, echopraxia, and additional pediatric-specific items(e.g.,refusal to eat/drink, social withdrawal, incontinence, acrocyanosis, schizophasia, automatic compulsive movements). Higher scores indicate greater severity of catatonia. Mean change in total PCRS score from baseline (pre-intervention) to week 12. The PCRS is the primary efficacy measure of catatonic symptom severity. A ≥50% reduction from baseline is predefined as clinical response. between 30 to 50 % reduction from baseline is partial response. less than 30% reduction from baseline is predefined as non response
Time frame: Baseline, immediately post-benzodiazepine challenge (30 minutes after midazolam administration), Week 2, Week 4 , Week 8, and Week 12 (end of 3-month follow-up)
Change in Aberrant Behavior Checklist (ABC) Score
he Aberrant Behavior Checklist (ABC) is a caregiver-rated instrument designed to assess problem behaviors in individuals with developmental disabilities, including those with autism spectrum disorder. It consists of 58 items rated on a 4-point scale (0 = not at all a problem to 3 = problem is severe), yielding five subscale scores: Irritability, Agitation, Crying (15 items) Lethargy/Social Withdrawal (16 items) Stereotypic Behavior (7 items) Hyperactivity/Noncompliance (16 items) Inappropriate Speech (4 items) Higher subscale and total scores indicate greater severity of aberrant behaviors. In this study, the ABC (Community version or equivalent adapted for caregiver report) will be used to evaluate broader behavioral improvements, including challenging behaviors such as irritability, aggression, self-injury, and social withdrawal, which are common in profound autism with catatonic features. An Arabic-translated version (with author permission obtained) will be administered. This se
Time frame: Baseline, Week 2, Week 4, Week 8, and Week 12 (end of 3-month follow-up)
Response rate to benzodiazepine challenge test
Proportion of participants showing \>50% reduction in PCRS total score 30 minutes after intranasal midazolam challenge (0.15 mg/kg, max 10 mg). Positive response defines benzodiazepine responders who continue on oral clonazepam; negative response leads to ECT pathway.
Time frame: 30 minutes post-challenge (single time point)
Proportion of participants requiring electroconvulsive therapy (ECT)
Percentage of participants who fail the benzodiazepine challenge (\>50% PCRS reduction) or who fail to maintain ≥50% PCRS improvement after 1 month of maximum-dose oral clonazepam (up to 8 mg/day) and are therefore shifted to bilateral bitemporal ECT.
Time frame: Up to week 4 (decision point for ECT initiation)
Incidence of adverse events
Frequency and severity of all adverse events (including sedation, hypotension, and any other treatment-related events) occurring during benzodiazepine challenge, oral clonazepam titration/maintenance, or ECT sessions. Events are actively monitored and recorded at every study visit and during ECT procedures.
Time frame: Baseline through week 12 (continuous monitoring)
Plan to share: No — No plan to share individual participant data (IPD). This is a small, single-site open label pilot study conducted as part of an MD thesis at Tanta University, Egypt, involving a vulnerable population of adolescents with profound autism and catatonia. Due to privacy concerns, small sample size, potential for re-identification, and absence of a dedicated secure data repository or funding for de-identification and controlled access, IPD will not be made available to other researchers. Aggregate results will be published in scientific journals and/or a thesis, and summary data may be shared upon reasonable request to the principal investigator after publication, subject to ethics committee approval and data protection requirements.
No publications or documents are linked to this record.
Started Jan 2026 (actual). Primary completion is estimated for Aug 2026, 7 months after the start.
Of 800 non-industry interventional studies with no phase under Autism Spectrum Disorder, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 48. This study's planned 7 months is below that.
Counting every sponsor, half of 823 studies reached it within 25 months; a quarter within 12 and three quarters within 47.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Midazolam · Clonazepam