SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03514784

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Road to Discovery for Combination Probiotic BB-12 With LGG (Different Doses) in Treating Autism Spectrum Disorder Disorders

This protocol is a blinded randomized controlled study of the effects of BB-12 with LGG at different doses in 70 healthy children with autism spectrum disorders at lower and higher doses over an 56-day period and a 28- day observation period. The study is being conducted in order to assess safety and tolerability of the probiotic (BB-12 with LGG) at 2 different doses of BB-12 with LGG. Identifying effects on behaviors in healthy children with ASD using SRS-2 and ABC, GI symptoms using GI symptom severity index, and relevant biomarkers of inflammation, microbiota, and metabolites. Primary testing and procedures will be conducted at the University of Texas Health Science Center at Houston and Memorial Hermann Clinical Research Center. Biomarker identification includes Integrative analysis of plasma metabolome and stool microbiota will be conducted with the collaboration of Dr. Ruth Ann Luna and Dr. Jim Versalovic at Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology of Baylor College of Medicine.

NCT03514784 Autism Spectrum Disorder Gastrointestinal Symptoms
MeSH: Disease Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive
HPO: Autism Autistic behavior

3 Interventions

Name: BB-12 with LGG (Higher Dose)

Description: BB-12 with LGG - Higher Dose (10 billion CFUs)

Type: Drug

BB-12 with LGG (Higher Dose)

Name: Placebo

Description: Maltodextrin

Type: Drug

Placebo

Name: BB-12 with LGG (Lower Dose)

Description: BB-12 with LGG - Lower Dose (1 billion CFUs)

Type: Drug

BB-12 with LGG (Lower Dose)


Primary Outcomes

Description: Adverse events (Safety) will be measured by case report form (survey) that are related to BB-12 with LGG (health-promoting bacteria) or placebo treatment. The symptom grade will detail the severity of adverse events.

Measure: Effects of BB-12+LGG at different doses on adverse events (safety)

Time: 84 days

Secondary Outcomes

Description: Psychological/Behavioral change in irritability and related maladaptive behaviors associated with ASD will be measured by the Aberrant Behavior Checklist (ABC) pre and post treatment

Measure: Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors with Aberrant Behavior Checklist (ABC)

Time: Days 1, 21, 56 and 84

Description: Psychological/Behavioral change in irritability and related maladaptive behaviors associated with ASD will be measured by the and the Social Responsiveness Scale-2 (SRS-2) pre and post treatment.

Measure: Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors measured with the Social Responsiveness Scale-2

Time: Days 1, 21, 56 and 84

Other Outcomes

Description: GI symptoms will be measured by the GI Severity Index.

Measure: Effects of BB-12+LGG at different doses on GI symptoms as measured by GI Symptom Severity Index

Time: Days 1, 21, 56 and 84

Description: Plasma S100A9 will indicate GI and systemic levels of inflammation. S100A9 is a damage-associated molecular pattern molecule (DAMP) released by granulocytes, which is reportedly elevated 2-fold in plasma of children with ASD.

Measure: Effects of BB-12+LGG at different doses on gut inflammation (S1009A)

Time: Days 1, 56 and 84

Description: Biological change in fecal calprotectin levels. FC is a highly accurate fecal marker of inflammation.

Measure: Effects of BB-12+LGG at different doses on gut inflammation (Fecal Calprotectin)

Time: Days 1, 56 and 84

Description: Plasma zonulin, a marker for intestinal permeability ("leaky gut"), which is often associated with inflammation.

Measure: Effects of BB-12+LGG at different doses on gut inflammation (Plasma Zonulin)

Time: Days 1, 56 and 84

Description: IL-8 can be an indicator of gut inflammation; it released from the intestinal epithelial cells during inflammation.

Measure: Effects of BB-12+LGG at different doses on gut inflammation (IL-8)

Time: Days 1, 56 and 84

Description: Using 16S rDNA analysis, this will determine microbial alpha and beta diversity and distribution of the major taxa before and after probiotic treatment.

Measure: Effects of BB-12+LGG at different doses on fecal microbial community

Time: Days 1, 56 and 84

Description: This will determine levels of metabolic markers which are reported to be abnormal in autism: fecal amino acids, ammonia, short chain fatty acids (SCFA), and phenols.

Measure: Effects of BB-12+LGG at different doses on metabolites

Time: Days 1, 56 and 84

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 S1009A

GI symptoms will be measured by the GI Severity Index.. Effects of BB-12+LGG at different doses on gut inflammation (S1009A). --- S1009A ---



HPO Nodes


HPO:
Autism
Genes 168
GABRB2 SOX2 MKRN3 SOX3 GABRD SNORD115-1 CACNA1A UBA5 CACNA1C ATP6V1A DPYD PIGL AARS HNF1B SATB2 MAGEL2 PDE4D DYM ZBTB20 TCF12 FMR1 WWOX HDAC4 COMT MAOA ARV1 ATRX CLIP2 SZT2 WFS1 SLC35C1 HCN1 KDM5C SMC1A NTRK2 BCKDK IQSEC2 NAGA HDAC8 KCNAB2 DYRK1A GATM IPW PWRN1 BAZ1B DHDDS GRIA3 FTSJ1 TSC1 TSC2 CNKSR2 NDN CHD7 NDP SIN3A PLXND1 GRIN2D REV3L SIM1 MED13L RFC2 RREB1 PTEN GTF2IRD1 SKI SLC1A2 CREBBP MECP2 YWHAG JMJD1C SHANK3 SH2B1 CHRNA7 SNORD116-1 HESX1 MEIS2 CYFIP2 OPHN1 NECAP1 TRAK1 HIRA MKRN3-AS1 EEF1A2 SYNGAP1 IL1RAPL1 LHX1 GJA5 GJA8 LIMK1 KLLN OTX2 GTF2I KCNA2 PPP3CA STS STXBP1 NLGN4X ADSL SEC24C COX1 ALMS1 KCNB1 COX2 COX3 SYNJ1 PROKR2 ARVCF SMC3 SETD5 UBE3A PIK3CA NFIB DHCR7 NUS1 ND1 SCN3A AP3B2 UFD1 ND4 ARNT2 ND5 CLTC ND6 PAH SCN8A NPAP1 ANKRD11 EHMT1 AUTS2 PRKAR1A FLCN KMT2A NHS SLC13A5 TRNF AKT1 FGF12 FGFR1 TRNH ELN TRNL1 RERE PWAR1 HERC2 TRNQ TRNS1 DNM1 TRNS2 TRNW PRDM16 ALDH5A1 NIPBL SNRPN SLC9A6 MED12 TBL2 EP300 SEC23B TBX1 SDHB RAI1 SDHC SDHD SMAD4 SEMA3E GP1BB RAD21 ALG13
Autistic behavior
Genes 282
GABRB2 SOX2 MKRN3 GABRB3 SOX3 GPHN GABRD SNORD115-1 UBA5 ATP6V1A RAB11B AARS CNNM2 PDE4D DYM ZBTB20 HIVEP2 PIGP WWOX FRMPD4 HDAC4 PSEN1 MAOA ACADL ATRX MICOS13 TMEM237 MAPT SLC35C1 NEXMIF KDM5C ZNF423 SMC1A ACOX1 BCKDK IQSEC2 TMEM216 NAGA HDAC8 ASH1L NAA10 GATM IPW PWRN1 DHDDS FTSJ1 SRY TSC1 CHD1 TSC2 CHD2 NDN RPS23 NDP PLXND1 RREB1 PTEN BCOR MECP2 MEF2C CHRNA7 SNORD116-1 HESX1 HNRNPH2 MEIS2 NDUFS4 DDX3X TBC1D24 HIRA SYNGAP1 CDKL5 KMT2C TUBB3 GJA5 GJA8 ARID1B KCNA2 NEUROD2 STXBP1 NLGN4X ADSL CLCN4 ALMS1 KCNB1 SYNJ1 NALCN PROKR2 ST3GAL5 UBE3A PIK3CA NFIB SQSTM1 HECW2 SCN1A DHCR7 PCDH19 SCN3A UFD1 ARNT2 CLTC SCN8A NPAP1 SYN1 SMG9 ALDH18A1 CC2D2A AP1S2 KMT2A PACS2 NHS AKT1 FGF12 FGFR1 GNAQ TAF1 PWAR1 HERC2 CAMTA1 TMEM231 DNM1 CLP1 ALDH5A1 NIPBL KCNT1 SLC9A6 MED12 FOXG1 SEC23B TBX1 SDHB SDHC AGTPBP1 VCP SDHD GP1BB RAD21 TBX2 TLK2 CACNA1A CACNA1C TCF4 DPYD C12ORF4 PIGL HNF1B SATB2 CUX2 MAGEL2 DEAF1 NAA15 TCF12 FMR1 RARS AFF2 COMT ARV1 CLIP2 MBOAT7 SZT2 WFS1 PUF60 PPM1D HCN1 NTRK2 CEP290 NDUFAF3 RNF135 KCNAB2 DYRK1A ARFGEF2 TMEM138 BAZ1B GRIA3 TWNK GRN CNKSR2 CHD7 SIN3A GRIN1 ST3GAL3 SPECC1L POMT1 GRIN2D REV3L SIM1 MED13L RFC2 GTF2IRD1 SKI ADNP SLC1A2 CREBBP YWHAG JMJD1C SHANK3 SH2B1 MSTO1 RSPRY1 ZFPM2 CYFIP2 OPHN1 NECAP1 CHMP2B TRAK1 MKRN3-AS1 EEF1A2 SLC6A1 IL1RAPL1 NDUFA13 LHX1 SLC6A8 TMEM106B PPP2CA SNX14 LIMK1 SETD2 SLC35A3 KLLN NDUFAF4 OTX2 GTF2I PPP3CA SLC25A12 STS EGF SEC24C COX1 COX2 COX3 ARVCF SMC3 KMT5B CTCF SETD5 SLC25A1 OTUD6B NUS1 ND1 AP3B2 ND4 ND5 CXORF56 ND6 PAH CNTNAP2 TREM2 ANKRD11 EHMT1 AUTS2 PRKAR1A FLCN SLC13A5 TRNF RORA DEPDC5 TRNH ELN TRNL1 RERE TBR1 TRNQ TBC1D23 ATP1A3 TRNS1 TRNS2 C9ORF72 TRNW MAPK10 GFM1 MCTP2 PRDM16 SNRPN STAG2 TBL2 EP300 CDH15 RAI1 SMAD4 PRODH SEMA3E SON ALG13