SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03831646

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Clinical, Psychological and Genetic Characteristics of Patients With Atopic Dermatitis and Psoriasis

Atopic dermatitis (AD) and psoriasis (PS) are chronic, relapsing dermatological disorders with a high rate of psychiatric co-morbid pathology represented with depression. Brain Derived Neurotrophic Factor (BDNF) belongs to the neurotrophin family and widely studied in pathophysiology of psychiatric and dermatological disorders. A biological stress response system by altered hypothalamic-pituitary-adrenal (HPA) axis as well hypothalamic-pituitary-gonadal (HPG) axis may contribute to dermatoses and psychiatric disorders development. Various factors including gender, genetic, psychological stress, socioeconomic factors also affect the course of dermatoses. A 10-week, case-control study evaluate clinical, psychological and biochemical parameters in AD and PS patients, and healthy control volunteers (HC) depending on gender and BDNF rs6265 gene polymorphism. All parameters are evaluated twice: at disease exacerbation (study baseline) and week 10. The following methods are conducted: assessment of dermatological status, using Scoring of Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI); assessment of depression and anxiety according to DSM-V criteria and with Hamilton Depression Rating Scale (HAM-D) and with Hamilton Anxiety Rating Scale (HAM-A); analysis of serum BDNF (ng/ml), cortisol (nmol/L), testosterone (ng/dL) and IgE levels (IU/ml, AD only); DNA extraction and genotyping of BDNF variants.The study will last during 4-5 months.

NCT03831646 Atopic Dermatitis Psoriasis
MeSH: Psoriasis Dermatitis Dermatitis, Atopic Eczema
HPO: Atopic dermatitis Eczema Eczematoid dermatitis Inflammatory abnormality of the skin Palmoplantar pustulosis Psoriasiform dermatitis


Primary Outcomes

Description: Assessment of atopic dermatitis severity is conducted using Scoring of Atopic Dermatitis (SCORAD) index. SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. SCORAD <23 - mild AD; SCORAD from 23 to 63 - moderate AD; SCORAD> 63 - severe AD.

Measure: Assessment of change in the severity of atopic dermatitis after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and at week 10

Description: Assessment of the psoriasis severity is conducted using Psoriasis Area and Severity Index (PASI). The patient's body is divided into four sections (head (H) (10% of a person's skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)). The percent of skin lesions of each area is assessed as follows: 0 (0% of involved area); 1 (< 10%); 2 (10-29%); 3 (30-49%); 4 (50-69%); 5 (70-89%); 6 (90-100%). Further, for each region, the intensity of 3 clinical signs is evaluated - redness, thickness and scaling and assessed as follows: 0 - no lesions,1 - easy, 2 - moderate, 3 - severe, 4 - very severe. The sum of all three severity parameters is calculated for each section, multiplied by the area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 0.3 for body, 0.4 for legs). PASI range is from 0 (no disease) to 72 (maximum disease). The severity of psoriasis is assessed as follows: PASI <20 - mild; PASI from 20 to 50 - moderate; PASI> 50 - severe

Measure: Assessment of change in the severity of psoriasis after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and at week 10

Description: Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28

Measure: Assessment of change in the severity of depression in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and week 10

Description: Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28

Measure: Assessment of the severity of depression in healthy controls (HC)

Time: At disease onset (study baseline)

Description: Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe

Measure: Assessment of change in the severity of anxiety in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and week 10

Description: Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe

Measure: Assessment of the severity of anxiety in HC

Time: At disease onset (study baseline)

Description: The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml

Measure: Evaluation of changes in serum immunoglobulin E (IgE, IU/ml) levels from study onset (baseline) at week 10 in atopic dermatitis patients

Time: At disease onset (study baseline) and week 10

Description: The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml

Measure: Analysis of serum IgE (IU/ml) levels in HC

Time: At disease onset (study baseline)

Description: Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used

Measure: Evaluation of changes in serum Brain Derived Neurotrophic Factor (BDNF, ng/ml) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used

Measure: Analysis of serum BDNF (ng/ml) levels in HC

Time: At disease onset (study baseline)

Description: The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L

Measure: Evaluation of changes in cortisol (nmol/L) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L

Measure: Analysis of serum cortisol (nmol/L) levels in HC

Time: At disease onset (study baseline)

Description: The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.

Measure: Evaluation of changes in testosterone (ng/dL) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.

Measure: Analysis of serum testosterone (ng/dL) levels in HC

Time: At disease onset (study baseline)

Description: DNA extraction and genotyping the BDNF rs6265 (Val66Met) gene polymorphism in AD, PS and HC

Measure: DNA extraction in AD, PS and HC

Time: At disease onset (study baseline)

Secondary Outcomes

Description: EAD and IAD patients will be divided into subgroups in accordance with BDNF gene polymorphism and gender with following assessment of SCORAD scores compared with baseline after conventional treatment at week 10 in each group using unpaired t-test

Measure: Assessment and comparison (Unpaired t-test) of SCORAD scores in extrinsic atopic dermatitis (EAD, IgE level above the normal) and intrinsic atopic dermatitis (IAD, normal IgE level) patients compared with baseline after conventional treatment at week 10

Time: At disease onset (study baseline) and week 10

Description: Psoriasis patients will be divided into subgroups in accordance with BDNF gene polymorphism and gender with following assessment of PASI scores compared with baseline after conventional treatment at week 10 in each group.

Measure: Assessment and comparison (Unpaired t-test) of PASI scores in psoriasis patients compared with baseline after conventional treatment at week 10 in accordance with BDNF gene polymorphism (Val/Val; Val/Met;Met/Met) and gender(males, females)

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of HAM-D scores in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of HAM-D scores in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-D scores in EAD, IAD, PS and HC

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of HAM-A scores in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of HAM-A scores in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-A scores in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of serum BDNF(ng/ml) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum BDNF levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum BDNF (ng/ml) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for comparisons of serum cortisol (nmol/L) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum cortisol levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum cortisol (nmol/L) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum testosterone levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC divided into BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, females) at study baseline and week 10

Measure: Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC in accordance with BDNF rs6265 gene polymorphism and gender

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of testosterone/cortisol ratio in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of testosterone/cortisol ratio in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of testosterone/cortisol ratio in EAD, IAD, PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Correlation analysis of dermatological, psychological and biochemical parameters in EAD, IAD and PS patients, and HC divided into groups in accordance with BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, femaes)

Measure: Correlation analysis of studied parameters in dermatological patients and HC

Time: At disease onset (study baseline) and week 10

Time Perspective: Prospective

Case-Control


There is one SNP

SNPs


1 V66M

DNA extraction and genotyping the BDNF rs6265 (Val66Met) gene polymorphism in AD, PS and HC. --- Val66Met ---



HPO Nodes


HPO:
Atopic dermatitis
Genes 7
CARD11 BRAF HSPA9 IFIH1 ZNF341 DOCK8 NEK9
Eczema
Genes 114
CYBB FLG KRT1 COL5A1 FLI1 COL5A2 EFL1 KRT9 ERCC2 TRAF6 ERCC3 CIB1 KRT16 CARMIL2 SRD5A3 WAS HDAC4 COMT WIPF1 DOCK8 HLA-DQB1 POLE HLA-DRB1 CYBC1 NCF1 RNF113A TMC6 HLCS DNAJC21 CASP8 SRP54 CASR NCF2 NCF4 MCCC2 LBR SIK3 RREB1 NSMCE3 SLC30A2 SHOC2 EDA NSUN2 NEK9 GINS1 JMJD1C ZAP70 MYSM1 STAT1 TGM5 PGM3 STAT3 RBCK1 HIRA RNU4ATAC MSN NOD2 IFIH1 ZNF750 LIG4 GTF2E2 CD3G PTPRC PIGA KANSL1 SEC24C MBTPS2 BRAF EDAR ARVCF SUOX ZNF341 MTHFD1 PIK3CA CD28 BTD SBDS HPGD TP63 SLCO2A1 EDARADD DHCR7 UFD1 FECH PAH TMC8 CSTA SMARCA2 MPLKIP GTF2H5 SMARCC2 GNA11 CARD11 RBM8A TRPM1 CTLA4 C5 TAF1 TNFRSF1B KDF1 IL2RA PCCA PCCB HSPA9 TBX1 CARD14 IL7 IL7R RAC1 GP1BB COL1A1 SPINK5 CYBA FOXP3
Eczematoid dermatitis
Genes 10
CYBB HPGD NCF2 SLCO2A1 STAT3 FLG NCF1 CYBA FOXP3 ZAP70
Inflammatory abnormality of the skin
Genes 311
CYBB IL10 IL10RA IL10RB TRAF3IP2 MYD88 IL12A IRF2BP2 NLRP12 SLC29A3 ERCC2 TRAF6 ERCC3 ERCC4 ERCC5 PRTN3 HDAC4 PSEN1 RIPK1 HLA-B PDGFRA CHST14 MNX1 ERAP1 HLA-DPA1 ABCA12 HLA-DPB1 PSENEN HLA-DQB1 GJB4 ENPP1 CTSC ESR1 HLA-DRB1 GJB6 SPTA1 CYBC1 SPTB B2M NCF1 RNF113A TMC6 PSMB4 SLC6A19 GATA1 PEPD BLNK PSMB8 GATA3 PSMB9 HLCS CLEC7A ITGA6 TCIRG1 DNAJC21 CDH23 SRP54 PTPN22 NCF2 NCF4 SMARCAD1 MCCC2 TMEM173 EXTL3 WNT4 GPR101 RREB1 ADA SLC30A2 ADA2 NSUN2 IL17F LYST NEK9 ITGB4 GINS1 KLRC4 GFI1 MYSM1 MEFV NLRC4 MEIS2 STAT1 TGM5 PGM3 STAT3 STAT4 HIRA RNU4ATAC FAM111B NOD2 JAK3 IFIH1 GJA1 GJB2 GJB3 PTPRC PNPLA1 PIGA MBTPS2 BRAF EDAR MSMO1 SULT2B1 CIITA SUOX PIK3CA CARD9 POMP NFE2L2 BTD AGA PIK3R1 HPGD EDARADD DHCR7 NFKB1 BTK NFKB2 UFD1 MIF FECH GLUL TMC8 FGA GTF2H5 AK2 CCR1 GNA11 C4A CACNA1G RBM8A HSD3B2 TRPM1 ADAM17 IL17RA C5 FGFR2 TAF1 COX4I2 UROS KDF1 KIT DNASE1L3 HSPA9 ALOX12B IL23R TBX1 CARD14 SDHA SDHB RAC1 SDHC KIF11 FERMT3 GP1BB COL1A1 SPINK5 FOXP3 FOXC2 VEGFC FLG KRT1 RAG1 COL5A1 FLI1 RAG2 COL5A2 KRT5 COL7A1 EFL1 NIPAL4 FAT4 KRT9 TCF3 KRT10 FLT4 KRT14 CIB1 KRT16 CARMIL2 HYOU1 SRD5A3 ANK1 WAS COMT KRT17 WIPF1 ADAMTS3 DSG1 DOCK8 POLE MPDU1 FERMT1 RBP4 IKBKG LAMA3 AIRE POR CASP8 LAMB3 XIAP CASP10 GJC2 CASR LAMC2 SLC39A4 APOA1 IL17RC LIPN CHD7 AIP NCSTN LBR PSTPIP1 H6PD SIK3 NR3C1 NSMCE3 CFI TEK FAS PAPSS2 SHOC2 ECM1 SP110 EDA RFX5 RFXAP CDK10 JMJD1C SHANK3 ZAP70 ABCC6 NLRP3 RBCK1 POLR3A SLC4A1 EPG5 TFRC MSN SDR9C7 TGFB1 TTC7A LHCGR RMRP ZNF750 TGM1 USP8 LIG4 GTF2E2 SH3PXD2B CD3G BCL11B IL36RN KANSL1 SEC24C EGFR ARVCF DCLRE1C ZNF341 LACC1 MTHFD1 IL12A-AS1 CD28 CCBE1 SBDS RFXANK TP63 SLCO2A1 IGHM BTNL2 CERS3 EBP NAXD TLR4 PAH PRKACA LPIN2 CSTA SMARCA2 MPLKIP LRRC8A ELANE SMARCC2 CYP4F22 CD79A CD79B UBAC2 ALOXE3 CARD11 CTLA4 IGLL1 TNFAIP3 TNFRSF1A TNFRSF1B KDSR CTSB IL1RN LYZ IL2RA PCCA PCCB IL2RG LMBRD1 IL6 EPB42 IL7 MVK IL7R CYBA
Palmoplantar pustulosis
Psoriasiform dermatitis
Genes 17
GATA3 TTC7A MSMO1 DSG1 FLI1 IRF2BP2 LIG4 HLA-DQB1 CACNA1G TP63 HLA-DRB1 SLC29A3 CTLA4 CARD14 NFKB2 IL36RN FOXP3