Clinical trial NCT02410902: A Trial of CM-AT in Children With Autism With All Levels of FCT (The Blum Study)
Official title: A Double Blind, Randomized, Placebo-Controlled Study of CM-AT for the Treatment of Autism in Children With All Levels of Fecal Chymotrypsin (FCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autism
Keywords: Autism
Lead sponsor: Curemark
Sponsor class: INDUSTRY
First posted: 2015-04-08
Enrollment: 190
Sex: ALL
Minimum age (years): 3
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether CM-AT is safe and effective in treating the core symptoms of autism in children with all levels of fecal chymotrypsin.

Detailed description: Autism is clearly a significant cause of disability in the pediatric population. Many children with Autism exhibit impaired protein digestion which may or may not manifest in self-restricted diets. The inability to digest protein affects the availability of essential amino acids in the body. CM-AT is designed to enhance protein digestion thereby potentially restoring the pool of essential amino acids. Essential amino acids play a critical role in the expression of several genes important to neurological function and serve as precursors to key neurotransmitters such as serotonin and dopamine. CM-AT is a proprietary enzyme that is designed as a granulated powder taken three times daily.

Eligibility criteria: Inclusion Criteria:

* Meets the current Diagnostic and Statistical Manual with Mental Disorders (DSM-IV-TR) for Autism (Autistic Disorder), screened by SCQ and confirmed by ADI-R;

Exclusion Criteria:

* Patient weighing \< 13kg (28.6 lbs)
* Previous allergy to porcine (pork) products
* Previous history of severe head trauma or stroke, loss of consciousness, seizure (or need for seizure medication either present or past) within one year of entering study or uncontrolled systemic disease
* Diagnosis of: HIV, cerebral palsy, endocrine disorder, pancreatic disease, muscular dystrophy, known genetic disorder, blood dyscrasia, ongoing GI disease
* Evidence of severe, moderate or uncontrolled systemic disease; and/or any co-morbid condition which in the Investigator's or Medical Director's opinion makes it undesirable for the subject to participate in the study or jeopardizes compliance with the protocol;
* Within 30 days of starting the study, certain supplementation, chelation or dietary restriction (a 30 day washout period would be required for inclusion);
* Ongoing dietary restriction for allergy or other reasons except nut allergies (lactose-free allowable);
* Use of of any stimulant medication must be discontinued 5 days prior to entering the study.
* Subject must have a stable dose of SSRI's for at least 30 days.
* Inability to ingest study drug and/or follow prescribed dosing schedule

Primary outcomes:
measure: Primary Outcome Measurements to Determine Efficacy of Treatment With CM-AT Versus Placebo for Changes in the Aberrant Behavior Checklist Subscale for Irritability / Agitation (ABC-I) Between Baseline and Week 12/Termination Visit
timeFrame: Screening through Week 12/Termination
Secondary outcomes:
measure: Secondary Outcome Measurements of Changes in the Aberrant Behavior Checklist Checklist Subscale for Lethargy / Social Withdrawal (ABC-L) Between Baseline and Week 12/Termination Visit
timeFrame: Screening through Week 12/Termination.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center (S.A.R.R.C.)
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Pediatrics Multidisciplinary Research Unit
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children'S Hosp. Research Institute (A.C.H.R.I.)
state: Arkansas
city: Orange
country: United States
facility: N.R.C. Research Institute
state: California
city: Sacramento
country: United States
facility: M.I.N.D. Institute (Univ.of California, Davis)
state: California
city: San Francisco
country: United States
facility: University of California (U.C.S.F.)
state: California
city: Centennial
country: United States
facility: IMMUNOe RESEARCH CENTERS
state: Colorado
city: New Haven
country: United States
facility: Yale Child Study Center
state: Connecticut
city: North Miami
country: United States
facility: Segal Institute For Clinical Research
state: Florida
city: Orange City
country: United States
facility: Florida Hospital Medical Group-Lake Mary Pediatrics
state: Florida
city: Orlando
country: United States
facility: Kaley Kildahl
state: Florida
city: Evansville
country: United States
facility: Research Institute of Deaconess Clinic
state: Indiana
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Shreveport
country: United States
facility: L.S.U. Health Sciences Center
state: Louisiana
city: Bingham Farms
country: United States
facility: Detroit Clinical Research Center, P.C.
state: Michigan
city: Egg Harbor Township
country: United States
facility: Children'S Specialized Hospital
state: New Jersey
city: Toms River
country: United States
facility: Children'S Specialized Hospital
state: New Jersey
city: Voorhees
country: United States
facility: Clinical Research Center of Nj
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Med.Center, Autism & Obsessive Compulsive Spectrum Prog.
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: Duke Center For Autism and Brain Development
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic, Center For Autism Research
state: Ohio
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Med.Center -Treatment & Research Inst. For Asd
state: Tennessee
city: Houston
country: United States
facility: University of Texas, Houston Dept. of Psychiatry and Behavioral Sciences
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia, Dept. of Psychiatry and Neurobehavioral Sciences
state: Virginia
city: Herndon
country: United States
facility: Neuroscience, Inc.
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic-Virginia Tech, Carilion School of Medicine
state: Virginia
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Deborah Pearson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Robert Hendren, DO
role: PRINCIPAL_INVESTIGATOR
References:
citation: McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, Veenstra-Vanderweele J. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics. 2011 May;127(5):e1312-21. doi: 10.1542/peds.2011-0427. Epub 2011 Apr 4.
citation: Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012 Mar 30;61(3):1-19.
citation: Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators; Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ. 2014 Mar 28;63(2):1-21.
citation: Peacock G, Amendah D, Ouyang L, Grosse SD. Autism spectrum disorders and health care expenditures: the effects of co-occurring conditions. J Dev Behav Pediatr. 2012 Jan;33(1):2-8. doi: 10.1097/DBP.0b013e31823969de.
citation: Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.
citation: McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83. doi: 10.1542/peds.2013-3995.
citation: Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18. doi: 10.1542/peds.2009-1878C.
citation: Samsam M, Ahangari R, Naser SA. Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance. World J Gastroenterol. 2014 Aug 7;20(29):9942-51. doi: 10.3748/wjg.v20.i29.9942.
citation: Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 2012 Jun;5(3):160-79. doi: 10.1002/aur.239. Epub 2012 Apr 11.
citation: Wasfy M, Oyofo B, Elgindy A, Churilla A. Comparison of preservation media for storage of stool samples. J Clin Microbiol. 1995 Aug;33(8):2176-8. doi: 10.1128/jcm.33.8.2176-2178.1995.
citation: Cavallini G, Benini L, Brocco G, Riela A, Bovo P, Pederzoli P, Angelini G, Pelle C, Bertelli G, Scuro LA. The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests. Pancreas. 1989;4(3):300-4. doi: 10.1097/00006676-198906000-00005.
citation: Matthews DM. Intestinal absorption of amino acids and peptides. Proc Nutr Soc. 1972 Sep;31(2):171-7. doi: 10.1079/pns19720033. No abstract available.
citation: Coutinho AM, Oliveira G, Morgadinho T, Fesel C, Macedo TR, Bento C, Marques C, Ataide A, Miguel T, Borges L, Vicente AM. Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry. 2004 Mar;9(3):264-71. doi: 10.1038/sj.mp.4001409.
citation: Naushad SM, Jain JM, Prasad CK, Naik U, Akella RR. Autistic children exhibit distinct plasma amino acid profile. Indian J Biochem Biophys. 2013 Oct;50(5):474-8.
citation: Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, Sosunov A, Sonders MS, Kanter E, Castagna C, Yamamoto A, Yue Z, Arancio O, Peterson BS, Champagne F, Dwork AJ, Goldman J, Sulzer D. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014 Sep 3;83(5):1131-43. doi: 10.1016/j.neuron.2014.07.040. Epub 2014 Aug 21.
citation: Balasubramanian MN, Butterworth EA, Kilberg MS. Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E789-99. doi: 10.1152/ajpendo.00015.2013. Epub 2013 Feb 12.
citation: Fairclough PD, Hegarty JE, Silk DB, Clark ML. Comparison of the absorption of two protein hydrolysates and their effects on water and electrolyte movements in the human jejunum. Gut. 1980 Oct;21(10):829-34. doi: 10.1136/gut.21.10.829.
citation: Arnold GL, Hyman SL, Mooney RA, Kirby RS. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003 Aug;33(4):449-54. doi: 10.1023/a:1025071014191.
citation: Munasinghe SA, Oliff C, Finn J, Wray JA. Digestive enzyme supplementation for autism spectrum disorders: a double-blind randomized controlled trial. J Autism Dev Disord. 2010 Sep;40(9):1131-8. doi: 10.1007/s10803-010-0974-2.
citation: Schreck KA, Williams K, Smith AF. A comparison of eating behaviors between children with and without autism. J Autism Dev Disord. 2004 Aug;34(4):433-8. doi: 10.1023/b:jadd.0000037419.78531.86.
citation: Bailey DB Jr, Raspa M, Olmsted M, Holiday DB. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A. 2008 Aug 15;146A(16):2060-9. doi: 10.1002/ajmg.a.32439.
citation: Lecavalier L. An evaluation of the Gilliam Autism Rating Scale. J Autism Dev Disord. 2005 Dec;35(6):795-805. doi: 10.1007/s10803-005-0025-6.
citation: Marcus RN, Owen R, Kamen L, Manos G, McQuade RD, Carson WH, Aman MG. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-1119. doi: 10.1097/CHI.0b013e3181b76658.
citation: Yerys BE, Wallace GL, Sokoloff JL, Shook DA, James JD, Kenworthy L. Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders. Autism Res. 2009 Dec;2(6):322-33. doi: 10.1002/aur.103.
citation: Schreck KA, Williams K. Food preferences and factors influencing food selectivity for children with autism spectrum disorders. Res Dev Disabil. 2006 Jul-Aug;27(4):353-63. doi: 10.1016/j.ridd.2005.03.005. Epub 2005 Jul 25.
citation: Borowitz D. Update on the evaluation of pancreatic exocrine status in cystic fibrosis. Curr Opin Pulm Med. 2005 Nov;11(6):524-7. doi: 10.1097/01.mcp.0000181474.08058.b3.
citation: Penn AH, Hugli TE, Schmid-Schonbein GW. Pancreatic enzymes generate cytotoxic mediators in the intestine. Shock. 2007 Mar;27(3):296-304. doi: 10.1097/01.shk.0000235139.20775.7f.
citation: Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2010 Aug 4;(8):CD004677. doi: 10.1002/14651858.CD004677.pub2.