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

Autism Spectrum Disorders Clinical Trial

— SAT1  

Official title:

The UCSD Suramin Autism Treatment-1 (SAT1) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02508259
• Other study ID #: 15-0134
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2015
• Est. completion date: April 2016

Study information

• Verified date: June 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autism Spectrum Disorders
• Autistic Disorder

Intervention

Drug:
• Suramin
20 mg/kg IV in 50 ml saline over 30 minutes
• Saline
50 ml IV over 30 minutes

Locations

Country	Name	City	State
United States	University of California, San Diego School of Medicine	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (5)

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:e400. doi: 10.1038/tp.2014.33. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Resource materials from the PI's lab website