Prednisone in Adults With an Immune-Mediated Subtype of Autism Spectrum Disorder

Christopher John McDougle, M.D.

Status and phase: Begins enrollment in 1 month; Early Phase 1

Conditions: Autism Spectrum Disorder

Treatments: Drug: Prednisone; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06934915

2024P003682

Details and patient eligibility

About

The goal of this clinical trial is to learn how prednisone affects adults with autism spectrum disorder (ASD). It will also learn about the safety of prednisone. The main questions it aims to answer are:

• How does prednisone affect the core features and associated target symptoms of ASD in adults with an immune-mediated subtype of ASD?
• Is prednisone safe for autistic adults without causing too many side effects?
• Does this study warrant larger trials studying anti-inflammatory drugs in this subject population?

Researchers will compare the drug prednisone to a placebo (a look-alike substance that contains no drug) to see how prednisone affects autistic adult males.

Participants will:

• Visit the clinic 2 times for a screening and baseline visit.
• Take prednisone or a placebo every day for 16 weeks.
• Visit the clinic 2 times for checkups, tests, questionnaires, and dose changes, and 1 time for a follow-up visit 4 weeks after stopping the study drug.
• Provide blood and urine samples for testing up to 4 times.
• Complete 8 remote calls every 1-2 weeks for checkups and dose changes.
• Keep a diary of the dose and times they take the study drug every day and any symptoms or side effects they experience.

Full description

• Randomized, double-blind, placebo-controlled, parallel-groups, flexibly dosed trial of prednisone in adults with autism spectrum disorder (ASD). Eligible participants will be randomized 1:1 prednisone or placebo.
• Participants will attend up to 5 in-person study visits at screening, baseline, Week 5, Week 10, and Week 20 (post-discontinuation follow-up).
• Interim dose adjustments will be determined during 8 scheduled remote visits at Weeks 1-4, Week 7, Week 12, Week 14, and Week 16.
• Blood and urine specimens will be collected at screening, Week 5, Week 10, and Week 20 for safety and biomarker assessments.

Enrollment: 32 estimated patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18 to 50 years of age (inclusive) and assigned male at birth.

2. Diagnostic Statistical Manual of Mental Disorders (DSM), Fourth Edition, Text Revision (DSM-IV-TR) diagnosed autistic disorder, and DSM, Fifth Edition, Text Revision (DSM-5-TR) diagnosed autism spectrum disorder (ASD), level 2 or 3. A qualified (board-eligible or board-certified) psychiatrist or psychologist, with experience in diagnostic determinations of ASD, will make a final diagnostic determination based on clinical history, clinical observations, medical records, mental status exams, and screening measures.

3. A Clinical Global Impression-Severity (CGI-S) rating ≥ 4 ("Moderate") at screening (and baseline).

4. A non-verbal IQ in the range of moderate intellectual disability or higher (≥ 35), as measured by the non-verbal Abbreviated IQ (ABIQ) score of the Stanford Binet Intelligence Scales, Fifth Edition (SB-5), or mental age of at least 18 months, as measured by the Cognitive and Adaptive Behavior subscales of the Developmental Profile (DP-4) Parent/Caregiver Interview form.

5. Participation of a study partner who has consistent contact with the participant and is willing and able to attend visits, oversee the participant's compliance with the protocol and study medication, and report on the participant's status through study assessments.

6. Participant reports ≥ 1 of the following:

   • A diagnosed comorbid autoimmune disease (e.g., Crohn's disease, Graves' disease, Hashimoto's disease, psoriasis, rheumatoid arthritis, ulcerative colitis, type 1 diabetes mellitus, etc.).
   • Current biomarker evidence of critical indicators of inflammation/autoimmunity, such as elevated levels of C-reactive protein (CRP) or abnormal value of antinuclear antibodies (ANA).
   • A significant family history of autoimmunity, defined as having ≥ 1 first-degree relative or ≥ 2 second-degree relatives with autoimmune diseases. The Principal Investigator (PI) will make the final determination on this criterion.

7. Participant reports a history of ≥ 2 of the following conditions or complaints:

   • Gastrointestinal symptoms
   • Epilepsy or seizures
   • Ear tube placements
   • Sleep disorder or difficulty sleeping

8. Any concomitant medications or interventions for ASD-related symptoms (e.g., alpha-2 agonists, anticonvulsants, antidepressants, antipsychotics, anxiolytics, gastrointestinal medications, medications for sleep disorders, probiotics, stimulants, behavioral therapies, psychosocial interventions, speech therapy, etc.) have been stable for at least 4 weeks prior to the screening visit and the participant/study partner intend to maintain a stable regimen throughout the trial.

9. Participant can tolerate swallowing large capsules.

10. Participant is willing and able, in the investigator's opinion, to comply with all study procedures.

Individuals must satisfy the following criteria to be enrolled as study partners:

1. The study partner is fluent in English.
2. The study partner is a caregiver or an individual who has consistent contact with the participant, knows the participant well, and is willing and able to attend visits, oversee the participant's compliance with the protocol and study medication, and report on the participant's status through study assessments. The PI will make the final determination on this criterion.

Exclusion criteria

1. DSM-5-TR diagnosed ASD, level 1, or presence of another DSM-IV-TR diagnosed pervasive developmental disorder, such as Asperger's disorder, childhood disintegrative disorder, Rett syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS). A qualified psychiatrist or psychologist will make a diagnostic determination after reviewing clinical history, clinical observations, medical records, mental status exams, and screening measures.
2. A CGI-S rating < 4 at screening (or baseline).
3. A non-verbal IQ in the range of severe or profound intellectual disability (< 35), as measured by the non-verbal ABIQ score of the SB-5, or mental age below 18 months, as measured by the Cognitive and Adaptive Behavior subscales of the DP-4 Parent/Caregiver Interview form. Individuals testing below 18 months may be enrolled after a case review by the PI and study psychologist, especially if testing scores were likely underestimated due to uncooperative behavior.
4. Previous documentation of a prolonged electroencephalogram (EEG) suggestive of Landau-Kleffner syndrome or continuous spike and wave during sleep (CSWS) syndrome.
5. Presence of a defined genetic disorder, such as Angelman syndrome, Fragile X syndrome, Noonan syndrome, Tuberous sclerosis, Williams syndrome, or any documented chromosomal or genetic abnormality with proven clinical significance in the etiology of ASD.
6. Documented significant pre- or post-natal central nervous system insult, such as an in-utero cerebral vascular accident, that is believed to have significantly contributed to the development of the individual's ASD.
7. Mitochondrial disorder verified by skin and/or muscle biopsy.
8. History of bipolar disorder or psychotic disorder, including major depressive disorder with psychotic features, schizoaffective disorder, or schizophrenia. History of a significant and interfering comorbid major psychiatric disorder, including obsessive-compulsive disorder, post-traumatic stress disorder, or substance use disorder requiring > 1 psychiatric hospitalization for treatment of specific comorbid psychiatric disorders above and beyond target symptoms associated with ASD, such as aggression, irritability, self-injury, property destruction, mood swings, or severe tantrums. Minor psychiatric disorders, such as adjustment disorder, attention-deficit hyperactivity disorder, generalized anxiety disorder, major depressive disorder, persistent depressive disorder, or social anxiety disorder, may not exclude participation. The PI will make the final determination on this exclusion criterion.
9. Concomitant medications or interventions for ASD-related symptoms (e.g., alpha-2 agonists, anticonvulsants, antidepressants, antipsychotics, anxiolytics, gastrointestinal medications, medications for sleep disorders, probiotics, stimulants, behavioral therapies, psychosocial interventions, speech therapy, etc.) have not been stable for at least 4 weeks prior to the screening visit.
10. An active bacterial, fungal, helminthic, protozoan, or viral infection that could be exacerbated by a course of prednisone, as determined by the PI.
11. Significant medical findings from history, physical examination, or laboratory testing that may be incompatible with prednisone use (e.g., participants with chronic infectious conditions or unstable diabetes mellitus).
12. Individuals with a history of seizures being treated with an anticonvulsant may be eligible if seizure-free for at least 6 months and the anticonvulsant dose has been stable for at least 4 weeks prior to the screening visit.
13. Use of immunosuppressive agents within the 6 months prior to the screening visit or concurrent use of immunosuppressive agents that, in the judgment of the PI, would interfere with study outcomes or pose unreasonable risk with prednisone administration.
14. A known hypersensitivity to prednisone or any other component of the study product.
15. The participant is deemed unsuitable for any reason by the PI, including an inability to complete or comply with study requirements.

Individuals may be excluded from enrollment as study partners if either of the following criteria are met:

1. The study partner is not fluent in English.
2. The study partner is deemed unsuitable for any reason by the PI, including an inability to complete or comply with study requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Prednisone

Experimental group

Description:

Eligible participants will receive prednisone for up to 16 weeks. The treatment period consists of 3 structured phases: Dose Escalation (Weeks 1-5), Optimal Dose Maintenance (Weeks 6-10), and Gradual Dose Reduction (Weeks 11-16).

Treatment:

Drug: Prednisone

Placebo

Placebo Comparator group

Description:

Eligible participants will receive a matching placebo for up to 16 weeks. The treatment period consists of 3 structured phases: Dose Escalation (Weeks 1-5), Optimal Dose Maintenance (Weeks 6-10), and Gradual Dose Reduction (Weeks 11-16).

Treatment:

Drug: Placebo