Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study is designed to test the safety and efficacy of a single, intravenous dose of suramin in autism spectrum disorders (ASD).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Suramin | Active Comparator | 20 mg/kg suramin in 50 ml of saline by intravenous infusion over 30 minutes |
|
| Saline | Placebo Comparator | 50 ml of saline by intravenous infusion over 30 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Suramin | Drug | 20 mg/kg IV in 50 ml saline over 30 minutes |
|
|
| 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 |
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert K Naviaux, MD, PhD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego School of Medicine | La Jolla | California | 92093 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25705365 | Background | 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. | |
| 24937094 | Background | 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. |
| Label | URL |
|---|---|
| Resource materials from the PI's lab website | View source |
Not provided
Safety, metabolomic, and completed outcome data will be made available to qualified institutional groups after peer review and publication.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Suramin | 20 mg/kg IV x1 |
| FG001 | Saline (Placebo) | IV Infusion x 1 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Male subjects with autism spectrum disorder (ASD), ages 4-17 years
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Suramin | 20 mg/kg IV x 1 |
| BG001 | Saline (Placebo) | IV infusion x 1 |
| BG002 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Patients receiving either suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 6 weeks compared to baseline |
|
6 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Suramin | 20 mg/kg IV x 1 | 0 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert K. Naviaux, MD, PhD | University of California, San Diego School of Medicine | 619-543-2904 | naviaux@ucsd.edu |
Not provided
| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D013498 | Suramin |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D009282 | Naphthalenesulfonates |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Saline | Drug | 50 ml IV over 30 minutes |
|
|
| 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 |
| 23516405 | Background | 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. |
| 23981537 | Background | 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. |
| 28695149 | Background | 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. |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 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. | Mean | Standard Deviation | units on a scale |
|
|
|
|
| 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. | Subjects receiving either suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 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. | Subjects receiving either suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 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. | Subjects receiving either suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 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. | Subjects receiving either suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 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. | Subjects receiving suramin or saline. | Posted | Mean | Standard Deviation | units on a scale | 6 weeks compared to baseline |
|
|
|
|
| 5 |
| 0 |
| 5 |
| 5 |
| 5 |
| EG001 | Saline (Placebo) | IV Infusion x 1 | 0 | 5 | 0 | 5 | 4 | 5 |
| Upper respiratory tract infection (URI) | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | In 7-year old after pizza and slushee consumption after playing youth league basketball, and in a 6-year old after a car ride. |
|
| Hyperactivity | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment | Both cases occurred 6-weeks after the infusion, after several days of a URI and fasting before lunch for the blood draw. Hypoglycemia was asymptomatic and corrected after a normal lunch. |
|
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
Not provided
Not provided
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D011083 | Polycyclic Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |