University of California, San Diego (UCSD) Suramin Autism Treatment-1 (SAT1) Trial

Study Overview
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Brief Summary
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This study is designed to test the safety and efficacy of a single, intravenous dose of suramin in autism spectrum disorders (ASD).

Detailed Description
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This study is designed to test a new theory of the origin and treatment of ASD. In this theory, ASD is caused by both genes and environment interacting to produce a persistent cell danger response (CDR; Naviaux RK, 2014) that interferes with and alters normal child brain development. Gut microbiome and immune systems are also affected. In this theory, the pathological persistence of the cell danger response is traceable to mitochondria, and maintained by purinergic signaling mediated by the release of extracellular nucleotides like adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine triphosphate (UTP), and uridine diphosphate (UDP). Suramin inhibits excess purinergic signaling by acting as a competitive inhibitor of nucleotide signaling at both ionotropic purinergic (P2X) receptors, and G-protein coupled, metabotropic purinergic (P2Y) receptors. Suramin has been found to correct the symptoms, metabolism, and brain synaptic abnormalities in two classical genetic and environmental mouse models of autism (Naviaux JC, et al. 2015; Naviaux JC, et al. 2014; Naviaux RK, et al. 2013). This study will test the safety and efficacy of a single dose of suramin in children with ASD. While it is not anticipated that a single dose will produce benefits for more than a few weeks, if successful, this study may lead to the development of newer and safer drugs for autism treatment.

Official Title
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The UCSD Suramin Autism Treatment-1 (SAT1) Trial

Conditions
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Autism Spectrum Disorders

Intervention / Treatment
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* Drug: Suramin
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Autism diagnostic observation schedule (ADOS) score of ≥ 7 Diagnosis of autism spectrum disorder by Diagnostic and Statistical Manual, 5th edition (DSM-V) Stable treatment and diet regimen for ≥ 2 months Resident of San Diego region Exclusion Criteria: Any prescription medications Hospitalization within the previous 2 months Active medical problem such as seizures, heart, liver, kidney, or adrenal disease Planning to start a new drug, diet, or behavioral intervention during the study Weight under the 5th percentile for age Unable to tolerate venipuncture, urine collection, or an indwelling intravenous catheter for 3-4 hours Plasma creatinine ≥ 1.4 mg/dl Liver function alanine amino transferase (ALT) or aspartate amino transferase (AST) ≥ 1.5-fold above the upper limit of normal Known intolerance to suramin or other antipurinergic drugs Unable to perform or cooperate with study requirements

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Suramin<br>20 mg/kg suramin in 50 ml of saline by intravenous infusion over 30 minutes | Drug: Suramin<br>* 20 mg/kg IV in 50 ml saline over 30 minutes<br>* Other names: Germanin;|
| Placebo Comparator: Saline<br>50 ml of saline by intravenous infusion over 30 minutes | Drug: Saline<br>* 50 ml IV over 30 minutes<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Autism Diagnostic Observation Schedule, 2nd Edition (ADOS2) | ADOS2 comparison scores are units on a scale of 0-10. A score of 7-10 was required for enrollment. A score of 7-10 is diagnostic for autism spectrum disorder (ASD). The higher the score, the more severe the core symptoms of autism spectrum disorder. Scores of 6 and below are considered off the ASD spectrum. | 6 weeks compared to baseline | 
| Expressive Language | Expressive One Word Picture Vocabulary Test (EOWPVT) scores are normalized for age. Typical language development produces a mean score of 100 with a standard deviation of 15. Outcomes for EOWPVT were expressed as the mean of the child-specific difference before and 6-weeks after treatment. For example, if the 6-week standard EOWPVT score was 59.6 and the baseline score was 63.8, the difference is -4.2 (= 59.6 - 63.8). A decrease in score at 6 weeks would corresponds to a decrease in language performance, while an increase, a positive difference, would reflect an increase. | 6 weeks compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aberrant Behavior Checklist (ABC) | The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. Stereotypy is reported, and scores range from 0 to 21, with higher scores indicating worse behavior. A negative difference corresponds to decreased symptoms after treatment. A positive difference corresponds to increased symptoms after treatment. | 6 weeks compared to baseline | 
| Autism Treatment Evaluation Checklist (ATEC) | The reported value is the Language sub-score of the ATEC, and the range for the language sub-score is 0-20. The higher the score, the worse the disability. Outcomes were measured at 6 weeks after treatment compared to baseline. A negative difference corresponds to a decrease in language disability, i.e an improvement in speech and language. A positive difference reflects an increase in language disability, i.e. a decrease in speech and language. | 6 weeks | 
| The Clinical Global Impression - Improvement Scale (CGI-I) | The CGI-I is scale that ranges from 1-7, reflecting the change in core autism behaviors after treatment. 1 is much improved, 4 is unchanged, and 7 is much worse. | Overall ASD symptoms at 6 weeks | 
| Repetitive Behavior Questionnaire | Total repetitive behavior was assessed using the Repetitive behavior questionnaire (RBQ), which has a scale from 0-87. Higher scores correspond to more severe repetitive behavior. Outcomes were analyzed as the difference in the score 6 weeks after treatment compared to baseline. A negative difference corresponds to improved behavior compared to baseline. A positive difference corresponds to worse behavior. | 6 weeks compared to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitochondria, purinergic signaling, cell danger response