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

Randomized, Double-Blind, Placebo-Controlled, Parallel-Groups Trial of Prednisone in Adults With an Immune-Mediated Subtype of Autism Spectrum Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Autistic Disorder; Autism; Autism Spectrum Disorders
• Intervention / Treatment: Drug: Prednisone; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Olivia M DeMichaelis; Phone Number: 781-860-1711; Email: MGHPREDICT-ASD@mgb.org
• Study Contact Backup: Name: Colleen G Buckless; Phone Number: 781-860-1711; Email: MGHPREDICT-ASD@mgb.org

Study Locations

• United States
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421
      • Recruiting
      • MGH Lurie Center for Autism
      • Principal Investigator: Christopher J McDougle, M.D.
      • Contact: Olivia DeMichaelis; Phone Number: 781-860-1711; Email: MGHPREDICT-ASD@mgb.org
      • Contact: Colleen G Buckless; Phone Number: 781-860-1711; Email: MGHPREDICT-ASD@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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. 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.
8. Participant can tolerate swallowing large capsules.
9. 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, psychotic disorder or schizophrenia.
9. History of one or more psychiatric hospitalizations due to symptoms of a major psychiatric disorder (e.g., major depressive disorder, OCD, PTSD, severe anxiety disorders, or substance use disorder). Hospitalization exclusively for irritability or behavioral dysregulation related to ASD, without evidence of a comorbid major psychiatric disorder, is permitted.
10. 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.
11. An active bacterial, fungal, helminthic, protozoan, or viral infection that could be exacerbated by a course of prednisone, as determined by the PI.
12. 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, defined as insulin-dependent or HbA1c >7.0).
13. 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.
14. 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.
15. A known hypersensitivity to prednisone or any other component of the study product.
16. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone; 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).	Drug: Prednisone; Starting dose: 5 mg daily. Maximum dose: 60 mg daily. Dosage forms: 5 mg, 10 mg, and 20 mg capsules.
Placebo Comparator: Placebo; 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).	Drug: Placebo; Capsules identical in size and appearance to those containing prednisone. Placebo capsules contain inactive ingredients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in Clinical Global Impressions-Improvement (CGI-I) ratings between the prednisone and placebo groups at Visit 9	Mean difference in CGI-I ratings between the prednisone and placebo groups at Visit 9 (efficacy). The CGI-I is a single-item measure of global symptomatic improvement compared to baseline. Improvement is rated on a 7-point scale, ranging from 1 ("Very much improved") to 7 ("Very much worse"). A global domain score of 1 ("Very much improved") or 2 ("Much improved") on the CGI-I scale will constitute a positive treatment response.	Baseline to Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of randomized study participants	Number of randomized study participants (feasibility).	At Baseline
Percent of participants enrolled at Visit 9 (Week 10) and contributing a visit 9 CGI-I rating	Percent of participants enrolled at Visit 9 (Week 10) and contributing a visit 9 CGI-I rating, irrespective of treatment continuation (feasibility).	Baseline to Week 10
Percent of participants randomized to prednisone experiencing serious adverse events (SAEs) probably or definitely related to medication	Percent of participants randomized to prednisone experiencing serious adverse events (SAEs) probably or definitely related to medication (safety).	Baseline to Week 20
Percent of participants randomized to prednisone who complete a ten-week course of study drug	Percent of participants randomized to prednisone who complete a ten-week course of study drug (tolerability).	Baseline to Week 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Irritability Subscale Score of the Aberrant Behavior Checklist-Community (ABC-C)	Change in ABC-C Irritability subscale score from Baseline to Week 10. The ABC-C is a 58-item, informant-based scale measuring psychiatric symptoms and behavioral disturbance across five domains (subscales) within the past 28 days. Each item is rated from 0 ("Not a problem") to 3 ("Severe problem"). The Irritability subscale assesses irritability, aggression, self-injury, and negative emotional states. Scores range from 0 to 45, with higher scores indicating more severe irritability symptoms.	Baseline to Week 10
Change in Social Withdrawal Subscale Score of the ABC-C	Change in ABC-C Social Withdrawal subscale score from Baseline to Week 10. The ABC-C is a 58-item, informant-based scale measuring psychiatric symptoms and behavioral disturbance across five domains (subscales) within the past 28 days. Each item is rated from 0 ("Not a problem") to 3 ("Severe problem"). The Social Withdrawal subscale assesses social avoidance, reduced emotional responsiveness, and lethargy. Scores range from 0 to 48, with higher scores indicating more severe lethargy and social withdrawal symptoms.	Baseline to Week 10
Change in Stereotypic Behavior Subscale Score of the ABC-C	Change in ABC-C Stereotypic Behavior subscale score from Baseline to Week 10. The ABC-C is a 58-item, informant-based scale measuring psychiatric symptoms and behavioral disturbance across five domains (subscales) within the past 28 days. Each item is rated from 0 ("Not a problem") to 3 ("Severe problem"). The Stereotypic Behavior subscale assesses repetitive, stereotyped movements and mannerisms. Scores range from 0 to 21, with higher scores indicating more severe stereotypic behavior symptoms.	Baseline to Week 10
Change in Hyperactivity/Noncompliance Subscale Score of the ABC-C	Change in ABC-C Hyperactivity/Noncompliance subscale score from Baseline to Week 10. The ABC-C is a 58-item, informant-based scale measuring psychiatric symptoms and behavioral disturbance across five domains (subscales) within the past 28 days. Each item is rated from 0 ("Not a problem") to 3 ("Severe problem"). The Hyperactivity/Noncompliance subscale assesses hyperactive and non-compliant behaviors. Scores range from 0 to 48, with higher scores indicating more severe symptoms of hyperactivity or noncompliance.	Baseline to Week 10
Change in Inappropriate Speech Subscale Score of the ABC-C	Change in ABC-C Inappropriate Speech subscale score from Baseline to Week 10. The ABC-C is a 58-item, informant-based scale measuring psychiatric symptoms and behavioral disturbance across five domains (subscales) within the past 28 days. Each item is rated from 0 ("Not a problem") to 3 ("Severe problem"). The Inappropriate Speech subscale assesses repetitive vocalizations, excessive talking, and other inappropriate speech behaviors. Scores range from 0 to 12, with higher scores indicating more severe inappropriate speech symptoms.	Baseline to Week 10

Collaborators and Investigators

• Sponsor: Christopher John McDougle, M.D.
• Investigators: Principal Investigator: Christopher J McDougle, M.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Neuroinflammation; Autism; Autoimmunity; Autism Spectrum Disorder; Autistic Disorder; Glucocorticoids; Autoimmune Disorders; Prednisone; Anti-Inflammatory Agents; Corticosteroids
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Immune System Diseases; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Pathological Conditions, Signs and Symptoms; Autism Spectrum Disorder; Neuroinflammatory Diseases; Autistic Disorder; Inflammation; Autoimmune Diseases; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone
• Other Study ID Numbers: 2024P003682

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to externally share IPD at this time, due to concerns regarding participant privacy, the risk of reidentification given the small and vulnerable study population, and limitations in the consent materials and protocol, which do not currently permit external data sharing. Institutional policy requires specific Data Use Agreements for any data sharing activity, and the study is protected by a Certificate of Confidentiality, further restricting disclosure of identifiable information. The research team may consider sharing de-identified data in the future, contingent upon publication of results and implementation of robust governance and approval mechanisms.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No