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

The UCSD Suramin Autism Treatment-1 (SAT1) Trial

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

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Suramin; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

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
Active Comparator: Suramin; 20 mg/kg suramin in 50 ml of saline by intravenous infusion over 30 minutes	Drug: Suramin; 20 mg/kg IV in 50 ml saline over 30 minutes; Other Names: Germanin
Placebo Comparator: Saline; 50 ml of saline by intravenous infusion over 30 minutes	Drug: Saline; 50 ml IV over 30 minutes; Other Names: Normal saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Robert K Naviaux, MD, PhD, University of California, San Diego

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Resource materials from the PI's lab website

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: mitochondria; purinergic signaling; cell danger response
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Anti-Infective Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Trypanocidal Agents; Suramin
• Other Study ID Numbers: 15-0134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Safety, metabolomic, and completed outcome data will be made available to qualified institutional groups after peer review and publication.