SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01795131

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Role of Vitamin B12 Supplementation During Pregnancy and Postpartum to Reduce Nutritional Anemia and Improve Immunity in Bangladeshi Women and Their Infants

Nutritional anemia is a major public health problem among children and women in developing countries. Despite ongoing national program of supplementing pregnant women with iron-folate, prevalence of anemia is 39% among pregnant women and 78% among infants in Bangladesh. Vitamin B12 deficiency is a more prevalent cause of megaloblastic anemia than folate in many developing countries. This data raises the interest to address the role of vitamin B12 deficiency in nutritional anemia. Low dietary intake of animal products, a predominant source of vitamin B12 may cause anemia. Besides maintaining normal erythropoiesis, B12 is essential for immune function. However, no studies have evaluated the effect of maternal B12 supplementation on reduction of anemia and improving immunity of their infants. The investigators hypothesize that vitamin B12 supplementation plus iron-folate during pregnancy and 3-mo postpartum would: (a) Decrease anemia among mothers and infants; (b) Improve vaccine specific cellular and humoral immune responses among mothers; (c) Improve vaccine specific immunity in infants by passive transfer; (d) Improve DNA methylation and one-carbon metabolism in mother-child pairs; (e) Reduce antenatal/postnatal depression. Results from this study will guide and provide support to the policy makers to identify effective strategies to reduce nutritional anemia in population at risk. The investigators aim to conduct a double-masked placebo controlled trial to investigate the added effect of vitamin B12 on the iron-folate supplementation among pregnant women. Anemic (Hb level <11.0 g/dl) mothers at 11-14 weeks of gestation will be randomized into two groups: supplement group will receive 250 ug vitamin B12 plus 400 ug folate and 60 mg iron; placebo group will receive folate and iron only. This daily supplementation will continue up to 3-mo postpartum. At 26-28 wk of gestation mothers will be given inactivated influenza vaccine. Data on anthropometric indices of mothers and children, birth size, infant growth and morbidity (mothers and children) throughout the study period will be recorded. 24-h dietary recall data will be collected from the mothers bimonthly throughout the study. Biochemical indicators of anemia including Hb, vitamin B12, ferritin, folate and α-glycoprotein (AGP) will be assessed in plasma of mothers (pre- and post-supplementation) and infants (cord blood and 3-months). Additional measurements include serum transferrin receptor (sTfR) in plasma and methyl malonic acid (MMA) and total homocysteine (tHcy) in the urine of mothers. Plasma vaccine specific antibody responses will be measured in mothers (pre- and post supplementation) and in infants (cord blood and 3-months). In breast milk, B12, folate and s-IgA will be determined. Genetic polymorphism (one-carbon metabolism) and DNA methylation will be studied in mothers and in cord blood.

NCT01795131 Nutritional Anemia in Mothers. Nutritional Anemia in Infants.
MeSH: Anemia
HPO: Anemia

2 Interventions

Name: Vitamin B12

Type: Dietary Supplement

Vitamin B12

Name: Placebo

Type: Dietary Supplement

Placebo


Primary Outcomes

Description: The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, sTfR, B12 levels in plasma. They will also measure urinary MMA and tHcy and B12 levels in breast milk.

Measure: a) Percent reduction in nutritional anemia among mothers (based on measurement of Hb, ferritin, sTfR, folate, B12 levels in plasma; urinary MMA and tHcy; B12 levels in breast milk.)

Time: 24 months

Description: Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.

Measure: Increase in influenza vaccine specific cellular and humoral responses among mothers (blastogenesis and T cell phenotyping,serum IgA, and IgG).

Time: 24 monnths

Description: Influenza vaccine-specific antibody responses (IgA, IgG) in plasma and colostrum/ breast milk [secretory IgA (s-IgA)] will be measured by ELISA. PBMC will be stimulated with Flu vaccine for blastogensis response.

Measure: Increase in influenza vaccine specific immunity in infants by passive transfer (vaccine specific IgG in cord blood and breast milk and IgA in children at 3 mo).

Time: 24 months

Description: The investigators will determine the percentage of nutritional anemia in mothers by measuring Hb, ferritin, B12 levels in plasma.

Measure: Percent reduction in nutritional anemia in infants (based on measurement of Hb, ferritin, B12 levels in plasma;

Time: 24 months

Secondary Outcomes

Description: Genomic DNA methylation will be measured by the methyl acceptance assay . Total homocysteine (tHcy) will be measured in urine samples by using HPLC with fluorimetric detection. Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing.

Measure: Effect of B12 status on DNA methylation and one-carbon metabolism in mother-child pairs.

Time: 24 months

Description: Participants will be interviewed on their mental status using the Centre for Epidemiological Studies-Depression questionnaire. The questionnaire contains 20 items comprising six major aspects of depression: depressed mood, hopelessness, worthlessness, fatigue, appetite and sleep disturbances. It has been previously used in rural and urban Bangladeshi women (J Hamadani) and found to correlate sensibly to children's growth and development. The interview will be conducted twice at the homes of the women first at baseline and at 3 mo postpartum.

Measure: Reduce depression scores

Time: 24 months

Purpose: Health Services Research

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 C677T

Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing.. Reduce depression scores. --- C677T ---

Mutations in the ALPL, MTHFR C677T and FUT2 genes will be determined by PCR- RFLP assay and DNA sequencing. --- C677T ---



HPO Nodes


HPO:
Anemia
Genes 468
EPHB4 CFH TACO1 TPP2 TSR2 EPO TMEM67 RPL26 RPL27 GLRX5 ABCA1 SLC29A3 ERCC2 RPL35A ABCB7 ERCC3 BRIP1 ERCC4 IRX5 HK1 HLA-B PDGFRA PDHA1 DNAJC19 MARS VPS45 NT5C3A HLA-DRB1 RPS7 RPS10 PEPD RPS14 RPS15A ETV6 TCIRG1 DNAJC21 MECOM RPS17 RPS19 IKZF1 ACTN4 EWSR1 HMGCL CD46 EXT2 RPS24 RPS26 TMEM173 RPS27 ACVR1 HMOX1 RPS28 RPS29 PFKM ACVRL1 F2 ADA ADAR LYST PGK1 ALX4 MYSM1 NLRC4 PHF21A PGM3 TNFRSF4 FANCA FANCC FANCD2 FANCE FANCB FANCF FANCG SAMD9L ICOS PIGA CLCN7 CLCNKB CIITA COG1 COG6 FDX2 HPGD SHPK HPRT1 RECQL4 FECH AGXT SNX10 PKLR SCO1 GTF2H5 AK1 CRIPT AK2 ALG8 UMPS NOP10 ALAD ALAS2 MMP1 MAD2L2 PLEC UROD UROS ALDOA SEC61A1 KDM6A HSPA9 SEC23B SDHA SDHB SDHC ALPL PML MPL COL4A1 FLI1 COL7A1 FOXRED1 KIF23 FMO3 COL17A1 NDUFAF5 ANK1 WAS WIPF1 OSTM1 CISD2 CTC1 WFS1 RRM2B POLG SMARCAL1 NDUFAF3 COX6B1 FERMT1 SLC19A2 LARS WT1 APC AIRE COX8A COX10 BIRC3 XIAP COX15 CP NLRP1 DGKE APOA1 CHD7 FASTKD2 IDH1 IDH2 CPOX NABP1 XRCC2 XRCC4 FANCM CFI FAS NHP2 FASLG CR2 SP110 COA8 ZAP70 SLC2A1 MMACHC SLC4A1 CASK MTFMT IFNG IFNGR1 LIPT1 PIGT TNFSF11 ACAD8 FAM111A GNA14 SLC12A3 LAT UBE2T G6PC3 IGH KLF1 MTHFD1 FARS2 PRF1 RFXANK SLCO2A1 HBB-LCR LPIN2 PRKACG MTR MPLKIP PRKAR1A PUS1 MTRR SMARCD2 PRKCD FOXP1 NDUFAF6 SMPD1 CTLA4 HAMP TRNN TRNS1 TRNW STX11 MUC1 IL2RA CTSK IL2RG G6PD LMBRD1 SLX4 MMUT MVK IL7R LYRM7 COX20 TET2 MYD88 UBR1 IL12B IFT140 NDUFS7 ZBTB16 ZBTB20 SAMD9 ATP7B PSAP GALT ACD ATRX TNFSF12 RTEL1 PET100 C15ORF41 PIEZO1 SPTA1 SPTB RNF113A VPS33A PSMB4 GATA1 PSMB8 PSMB9 CD55 GBA SRP54 NBN UNC13D DAXX SLC46A1 CCND1 DBH NDUFA2 NHLRC2 TNFRSF11A FTCD NDUFA4 ITGA2B CLPX NDUFA9 PTEN NDUFA10 GDF2 COQ2 NPHP4 ADA2 NSUN2 ITGB3 NDUFB8 ITGB4 NDUFS1 NDUFS2 ZBTB24 MMADHC PTH1R PLEKHM1 NDUFS3 PHGDH NDUFV1 NDUFS4 STAT1 ITK STAT3 NDUFS8 NDUFV2 STAT5B HELLPAR NOD2 STIM1 JAK2 CBLIF CDAN1 STK11 MALT1 BMPR1A SARS2 BPGM GLA NDUFA12 BRCA1 BRCA2 TINF2 GCLC SURF1 NFKB1 BTK DHFR NFKB2 SLC25A38 ABCD3 ABCD4 KCNN4 DKC1 PACS2 FIP1L1 ATP11C BCL10 RBM8A COX4I2 AMMECR1 NME1 KIT TALDO1 ABCG5 ABCG8 CA2 TBCE FERMT3 GP1BA PNP DNMT3B FOXP3 RAD51 RAD51C NPHP1 TBXAS1 GPI KRAS NPM1 SFXN4 RAG1 RAG2 SCO2 EFL1 KRT14 CAD RARA SLC11A2 AMN NRAS SRD5A3 MLX USB1 TCN2 NDUFAF2 CALR TMPRSS6 GPX1 NUMA1 SLC19A3 LAMA3 AGGF1 FARSB ABCB6 LAMB3 CASP10 DNM1L CASR LAMC2 FANCL REN ADAMTS13 OCRL LCAT CUBN WRAP53 SLC7A7 TYMP TEK MPIG6B LARS2 ECHS1 TERC TBL1XR1 TERT RFX5 RFXAP TF OPA1 PALB2 RHAG NLRP3 RFWD3 GSS YARS2 PNPO TFR2 TFRC TGFB1 TTC7A MMAA NDUFA13 RMRP RASGRP1 ORAI1 LIG4 GTF2E2 LIPA CD3G KMT2D TRNT1 THRA CD19 MS4A1 DCLRE1C CDCA7 AASS SBDS FANCI GYPC BTNL2 SCARB2 ISCU PRDX1 CD40LG ERCC6L2 TNFRSF13C CD59 ELANE TNFRSF13B STEAP3 CD81 PARN RPL35 TNFAIP3 GREM1 LRBA HBA1 HBA2 NHEJ1 HBB SH2D1A HBD MMAB ENG HBG1 PCCA HBG2 PCCB RPL5 EPB41 TP53 EPB42 RPL11 SMAD4 COX14 RPL15 PCNT RPL18 HELLS TPI1