A Proof-of-Concept Study of Minocycline in Autism

Study Overview
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Brief Summary
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The purpose of the study is to determine if Minocycline shows initial evidence of efficacy, safety, and tolerability in youth with Autism Spectrum Disorder ages 12 to 22 years.

Detailed Description
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This is a double-blind, placebo-controlled, crossover, proof-of-concept study that compares the pharmacodynamic and tolerability profiles of minocycline versus placebo in autism spectrum disorder.

Official Title
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Comparison of the Pharmacodynamic and Tolerability Profiles of Minocycline Versus Placebo in Autism Spectrum Disorder: a Double-blind, Placebo-controlled, Crossover, Proof-of-concept Study

Conditions
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Autism, Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 22 ≥ Age ≥12 years. Males and females included in study. Diagnostic confirmation of Autism Spectrum Disorder as confirmed by gold standard clinical interview using DSM 5 criteria and administration of the Autism Diagnostic Observation Schedule-2, Module 3 or 4. General good health as determined by physical exam, medical and psychiatric history and safety labs as defined by the PI or designee. Male study participants who are sexually active with a female partner of childbearing potential must be surgically sterilized, practicing abstinence, or agree to use highly effective methods of birth control (defined below), and not rely on barrier methods and spermicide alone, from the time of screening until 1 week after final dose of study drug. Female participants of childbearing potential may be included in the study provided they are practicing abstinence or are using a double barrier method from the time of screening until 1 week after the final dose of study drug. Participants using hormonal methods of birth control (oral, intravaginal, transdermal, injectable, or implantable) must be on a stable dose for at least three months prior to screening. Whole brain absolute cumulative gamma power (30 to 80 Hz) with median cut off at 2.5 (upward adjusted) Exclusion Criteria: Allergy or hypersensitivity to any of the tetracyclines antibiotics. Inability to swallow study drug. Concomitant use of scheduled anti-inflammatory drugs with the exception of as needed ibuprofen or acetaminophen use. Unstable dosing of any mood, anxiety or behavior medications in the 5 half-lives prior to Phase 1 baseline visit. Concomitant use of scheduled benzodiazepines, baclofen, gabapentin, pregabalin, or supplements with impact on the GABA system. Concomitant daily use of antacids Concomitant use of oral acne medications (isotretinoin), not including lotions or creams applied to the skin Concomitant use of any cannabinoid or related product. Unstable seizure disorder as defined by any seizure in the 6 months prior to baseline visit and/or a change in any anti-convulsant drug dosing in the 60 days prior to study screen. Abnormal baseline safety lab assessments including, but not limited to ALT or AST greater than 1.5x the upper limit of normal, elevated ANA, total bilirubin or creatinine greater than 1x the upper limit of normal, other clinically relevant lab abnormality, or abnormality in ECG, HR or BP at screening as determined by the investigator or designee. History of autoimmune disorder History of or current abuse of drugs or alcohol including prescription medication. Women who are pregnant (i.e. have a positive pregnancy test), intending to become pregnant, breast feeding, or women of child-bearing potential who are unwilling to use contraception as required in the study inclusion criteria or maintain abstinence during the course of the study Inability to attend scheduled study visits, plans for family relocation during the study, or any other criteria that the investigator may determine to be associated with inability to complete the study

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline versus Placebo<br>Phase 1: 4 weeks of daily minocycline 100mg BID dosing 2-week washout period Phase 2: 4 weeks of daily placebo dosing | Drug: Minocycline<br>* Minocycline 100 mg capsules or matching placebo will be prepared by the central investigational pharmacy at Cincinnati Children's Hospital Medical Center. Drug identity will be masked by over encapsulation of the study drug.<br>* Other names: Minocin;Drug: Placebos<br>* Minocycline 100 mg capsules or matching placebo will be prepared by the central investigational pharmacy at Cincinnati Children's Hospital Medical Center. Drug identity will be masked by over encapsulation of the study drug.<br>|
| Experimental: Placebo versus Minocycline<br>Phase 1: 4 weeks of daily placebo dosing 2-week washout period Phase 2: 4 weeks of daily minocycline 100mg BID dosing | Drug: Minocycline<br>* Minocycline 100 mg capsules or matching placebo will be prepared by the central investigational pharmacy at Cincinnati Children's Hospital Medical Center. Drug identity will be masked by over encapsulation of the study drug.<br>* Other names: Minocin;Drug: Placebos<br>* Minocycline 100 mg capsules or matching placebo will be prepared by the central investigational pharmacy at Cincinnati Children's Hospital Medical Center. Drug identity will be masked by over encapsulation of the study drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject weight will be compared pre- and post-treatment in the drug versus placebo conditions | Subject weight will be measured in kilograms | Through study completion, an average of 2 years | 
| Aberrant Behavior will be evaluated pre- and post-treatment in the drug versus placebo conditions | Aberrant behavior will be measured by the Aberrant Behavior Checklist total score | Through study completion, an average of 2 years | 
| Incidence of liver toxicity will be evaluated in the pre- and post-treatment setting in the drug versus placebo conditions | Liver toxicity will be defined as the development of an ALT or AST value greater than twice the upper limit of normal during a treatment period | Through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Autism Spectrum Disorder, Minocycline