Clinical trial NCT02508259: University of California, San Diego (UCSD) Suramin Autism Treatment-1 (SAT1) Trial
Official title: The UCSD Suramin Autism Treatment-1 (SAT1) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Autism Spectrum Disorders
Keywords: mitochondria
purinergic signaling
cell danger response
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2015-07-24
Enrollment: 10
Sex: MALE
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Autism Diagnostic Observation Schedule, 2nd Edition (ADOS2)
timeFrame: 6 weeks compared to baseline
measure: Expressive Language
timeFrame: 6 weeks compared to baseline
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC)
timeFrame: 6 weeks compared to baseline
measure: Autism Treatment Evaluation Checklist (ATEC)
timeFrame: 6 weeks
measure: The Clinical Global Impression - Improvement Scale (CGI-I)
timeFrame: Overall ASD symptoms at 6 weeks
measure: Repetitive Behavior Questionnaire
timeFrame: 6 weeks compared to baseline
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego School of Medicine
state: California
Study officials:
affiliation: University of California, San Diego
name: Robert K Naviaux, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Naviaux JC, Wang L, Li K, Bright AT, Alaynick WA, Williams KR, Powell SB, Naviaux RK. Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model. Mol Autism. 2015 Jan 13;6:1. doi: 10.1186/2040-2392-6-1. eCollection 2015.
citation: Naviaux JC, Schuchbauer MA, Li K, Wang L, Risbrough VB, Powell SB, Naviaux RK. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy. Transl Psychiatry. 2014 Jun 17;4(6):e400. doi: 10.1038/tp.2014.33.
citation: Naviaux RK, Zolkipli Z, Wang L, Nakayama T, Naviaux JC, Le TP, Schuchbauer MA, Rogac M, Tang Q, Dugan LL, Powell SB. Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. PLoS One. 2013;8(3):e57380. doi: 10.1371/journal.pone.0057380. Epub 2013 Mar 13.
citation: Naviaux RK. Metabolic features of the cell danger response. Mitochondrion. 2014 May;16:7-17. doi: 10.1016/j.mito.2013.08.006. Epub 2013 Aug 24.
citation: Naviaux RK, Curtis B, Li K, Naviaux JC, Bright AT, Reiner GE, Westerfield M, Goh S, Alaynick WA, Wang L, Capparelli EV, Adams C, Sun J, Jain S, He F, Arellano DA, Mash LE, Chukoskie L, Lincoln A, Townsend J. Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Ann Clin Transl Neurol. 2017 May 26;4(7):491-505. doi: 10.1002/acn3.424. eCollection 2017 Jul.