SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03859934

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Metabolic Effects of Melatonin Treatment

Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances such as insomnia or frequent awakenings are strong risk factors for T2DM with several studies indicating a central role of melatonin. Additionally, a certain single nucleotide polymorphism in the melatonin receptor gene, MTNR1B rs10830963, with an allele frequency of 30 %, is associated with increased fasting plasma glucose and T2DM. Due to treatment of, among other things, insomnia, the use of melatonin is increasing rapidly in Denmark with a 100-fold increase from 2007-2012 in children and adolescents. No previous studies have thoroughly assessed changes in glucose and fatty acid metabolism after 3 months of melatonin treatment in patients with T2DM.

NCT03859934 Metabolic Disease Insulin Sensitivity Glucose Metabolism Disorders (Including Diabetes Mellitus) Type 2 Diabetes Mellitus Blood Pressure Inflammation
MeSH: Diabetes Mellitus Inflammation Diabetes Mellitus, Type 2 Insulin Resistance Metabolic Diseases Glucose Metabolism Disorders
HPO: Diabetes mellitus Insulin resistance Type II diabetes mellitus

2 Interventions

Name: Melatonin

Description: Melatonin treatment

Type: Drug

Melatonin

Name: Placebo Oral Tablet

Description: Placebo treatment

Type: Drug

Placebo


Primary Outcomes

Description: Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min (mg of glucose to maintain euglycemia per kilogram of weight per minuts)

Measure: Change of insulin sensitivity

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment and compared afterwards with a paired T-tes

Description: Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)

Measure: Change of insulin secretion change

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: MTNR1a rs10830963 genotype influence on insulin sensitivity and insulin secretion (see outcome 1 + 2)

Measure: MTNR1a rs10830963 influence on change in insulin sensitivity and insulin secretion

Time: The outcome will be measured after 3 months of placebo treatment and again after 3 months of melatonin treatment

Description: Insulin signalling in muscle and adipose tissue assessed by western blot

Measure: Change of insulin signalling

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Secondary Outcomes

Description: Ambulatory blood pressure assessed with Mobil-O-graph, I.E.M., Stolberg, Germany (Unit: mmHg)

Measure: Change of ambulatory blood pressure

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Arterial stiffness assessed with Mobil-O-graph, I.E.M., Stolberg, Germany (unit: m/s)

Measure: Change of arterial stiffness

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Feces analysis of microbial mRNA

Measure: Change of gut microbiome

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Pittsburg Sleep Quality Index Questionnaire (Points on a scale: range 0-57)

Measure: Change of sleep evaluation 1

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Epworth Sleepiness Scale Questionnaire (Points on a scale: range 0-24)

Measure: Change of sleep evaluation 2

Time: After 3 months treatmentThe outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Major Depression Inventory Questionnaires (points on a scale: range 0-65)

Measure: Change of psychological health 1

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: World Health Organization 5 Questionnaires (points on a scale: range 0-25)

Measure: Change of psychological health 2

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Ghrelin, HbA1c, GLP-1, GLP-2, GIP, free fatty acids (FFA), leptin, cytokines, adiponectin, growth hormone, cortisol, hsCRP, CD163, MBL, IGF-1 and proinsulin measured by ELISA, RIA, or routine biochemical analysis. Unit: pmol/L

Measure: Hormonal changes

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Tracer technique with infusion of radioactive labeled glucose and palmitate for determination of rate of appereance. Unit: mikromol/min

Measure: Change of glucose and palmitate kinetics

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Forearm model with arteriovenous differences of glucose and palmitate (Arterial glucose minus venous glucose = forearm uptake (unit mmol/l). The same applies for palmitate

Measure: Change of regional glucose and palmitate uptake

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Evaluation of body composition and bone mineral density by DEXA-scan

Measure: Change of DEXA-scans

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Assessment of respiratory quotient (RQ) with indirect calorimetry (unit: VCO2/VO2)

Measure: Change of assessment of respiratory quotient (RQ)

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Description: Assessment of resting energy expenditure (REE) with indirect calorimetry (Unit J/s)

Measure: Change of assessment of resting energy expenditure (REE)

Time: The outcome will be measured after 3 months of placebo treatment and after 3 months of melatonin treatment

Purpose: Treatment

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 rs10830963

Additionally, a certain single nucleotide polymorphism in the melatonin receptor gene, MTNR1B rs10830963, with an allele frequency of 30 %, is associated with increased fasting plasma glucose and T2DM.

MTNR1a rs10830963 influence on change in insulin sensitivity and insulin secretion.

MTNR1a rs10830963 genotype influence on insulin sensitivity and insulin secretion (see outcome 1 + 2).

3. Does the MTNR1B rs10830963 risk allele alter the insulin secretion and insulin sensitivity compared with carries of the normal variant after chronic melatonin treatment?



HPO Nodes


HPO:
Diabetes mellitus
Genes 326
SOX2 MKRN3 SOX3 MKKS SNORD115-1 SPATA7 CDKN2A HFE CERKL UBR1 PRPF31 LRAT PRSS1 TREX1 PRSS2 IFT140 ARL2BP GLRX5 SLC29A3 MAK AHI1 ABCA4 PDE4D ZBTB20 PDE6A PDE6G ZMPSTE24 IMPDH1 CEL STUB1 SPINK1 RTEL1 PDE6B LEMD3 INS HLA-DQB1 GJB4 IFT172 AMACR KIZ CDHR1 HLA-DRB1 CYP19A1 CFTR DHX38 MAFA GAS1 INSR ZFP57 MC4R GATA3 CTRC GATA6 PDX1 IPW PEX1 BBS1 PWRN1 PEX6 BBS2 DNAJC21 PEX10 CDH23 SRP54 DHDDS NDN PRPF6 GCK NDP KCTD1 AGBL5 GPR101 PTCH1 HNF4A ADAR TTPA TUB SNORD116-1 HESX1 STAT1 STAT3 TULP1 BLK BLM ARL6 IFIH1 TTC8 GJA1 PROM1 NEK2 GJB3 SAG FBN1 NEUROD1 SARS2 PNPLA6 BRCA1 ALMS1 BRAF BRCA2 PROKR2 CLCNKB TINF2 KLHL7 REEP6 FAM161A PIK3R1 GLI2 ABCC8 KCNJ11 RNASEH2C ARNT2 NPAP1 SCAPER FSCN2 DCAF17 AHR PRCD DKC1 FGF8 PLAGL1 AKT2 NOP10 FGFR1 PLCD1 GNAS PWAR1 SEMA4A HERC2 MERTK FOXH1 PLIN1 HYMAI NODAL USH2A CLRN1 CNGB1 CNGA1 EIF2AK3 MOG CDON CA4 IMPG2 PDE11A FOXP3 FOXC2 HJV PROK2 RNASEH2B KRAS TCF4 KLF11 EFL1 HNF1A BEST1 HNF1B PNPLA2 NR2E3 MAGEL2 POC1A OFD1 SLC25A4 USB1 NRL CLIP2 APOA5 CISD2 RNASEH2A CTC1 PTF1A WFS1 GPR35 POLD1 FOS RRM2B POLG AGPAT2 RBP3 WRN SLC19A2 HGSNAT GLIS3 SHH AIRE KIAA1549 FUZ BAZ1B RDH12 POMGNT1 PRPH2 ARHGEF18 DNM1L CP TWNK CPA1 CASR PCARE SAMHD1 TDGF1 AIP CAV1 PSTPIP1 FXN APOE IDH3B PPARG RFC2 XRCC4 WRAP53 SIX3 GTF2IRD1 NSMCE2 PRPF8 DLL1 NHP2 TERC TERT EDA RGR SLC7A14 AR LEP OPA1 LEPR PALB2 POLR3A RHO CRB1 ZIC2 MKRN3-AS1 CRX RLBP1 TTC7A PPP1R3A CNBP MST1 ERGIC1 LHX1 TGIF1 USP8 MLXIPL LIG4 LIMK1 EYS ARL3 LIPE OTX2 IGF1R GTF2I HMGA2 ATP6 TRNC SLC12A3 LMNA COX1 COX2 COX3 GUCA1B IFT88 CYTB SLC16A2 PRPF4 PRPF3 ELMO2 PDE8B VANGL1 SBDS EIF2S3 IER3IP1 ZNF408 CIDEC ND1 ARMC5 ND4 ND5 ND6 PRKACA PRKAR1A NKX2-5 APPL1 TRNE TRNF ROM1 ZFYVE26 PARN CAVIN1 BSCL2 TRNH RP9 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM HAMP CTNS CTNNB1 C8ORF37 TRNQ TRNS1 TRNS2 POLG2 TRNV TOPORS TRNW KDSR HBB SUFU IL2RA RPE65 DNAJC3 SNRNP200 SNRPN PALLD TBL2 DISP1 EDA2R NEUROG3 TP53 CEP19 SMAD4 PCNT ZNF513
Insulin resistance
Genes 56
BLK PPP1R3A KLF11 HNF1A HNF1B IGF1 LIPE NEUROD1 IGFALS ZMPSTE24 SLC12A3 CEL LMNA ALMS1 CLCNKB PTF1A INS PIK3R1 POLD1 FOS ABCC8 CYP19A1 CIDEC KCNJ11 AGPAT2 INSR ZFP57 WRN DCAF17 GATA6 PDX1 MFN2 APPL1 PLAGL1 AKT2 CAVIN1 BSCL2 HSD3B2 DBH GCK LMNB2 PAX4 CAV1 HSD11B1 PPARG XRCC4 NSMCE2 PLIN1 HNF4A HYMAI EIF2AK3 LEP LEPR STAT3 CEP19 PMM2
Type II diabetes mellitus
Genes 152
MKRN3 SNORD115-1 SPATA7 CERKL PRPF31 LRAT KLF11 IFT140 HNF1A BEST1 HNF1B ARL2BP NR2E3 GLRX5 MAK AHI1 MAGEL2 ABCA4 PDE6A PDE6G IMPDH1 OFD1 STUB1 SPINK1 NRL CLIP2 PDE6B IFT172 AMACR KIZ CDHR1 CYP19A1 DHX38 INSR RBP3 WRN MC4R HGSNAT PDX1 IPW KIAA1549 PWRN1 BBS2 BAZ1B PEX10 RDH12 POMGNT1 PRPH2 DHDDS ARHGEF18 PCARE NDN PRPF6 GCK IDH3B AGBL5 RFC2 XRCC4 GTF2IRD1 PRPF8 RGR TUB SLC7A14 AR SNORD116-1 TULP1 POLR3A RHO CRB1 MKRN3-AS1 CRX BLM RLBP1 PPP1R3A ARL6 TTC8 PROM1 LIG4 NEK2 LIMK1 EYS ARL3 SAG FBN1 GTF2I PNPLA6 SLC12A3 LMNA COX1 ALMS1 BRAF COX2 COX3 GUCA1B CLCNKB IFT88 KLHL7 PRPF4 PRPF3 REEP6 FAM161A ABCC8 ZNF408 ND1 ND4 ND5 ND6 NPAP1 SCAPER FSCN2 AHR PRCD TRNE TRNF ROM1 AKT2 TRNH RP9 PLCD1 RP1 ELN TRNK PAX4 RP2 TRNL1 RPGR ATM PWAR1 SEMA4A CTNNB1 C8ORF37 HERC2 TRNQ MERTK TRNS1 TRNS2 TOPORS TRNW USH2A RPE65 CLRN1 CNGB1 CNGA1 SNRNP200 SNRPN TBL2 MOG CEP19 CA4 IMPG2 PCNT ZNF513