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Report for Clinical Trial NCT00887562

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes

The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.

NCT00887562 MELAS Syndrome
MeSH:MELAS Syndrome Brain Diseases Acidosis Acidosis, Lactic
HPO:Acidosis Encephalopathy Lactic acidosis Metabolic acidosis

3 Interventions

Name: Idebenone

Description: 900 mg/day for 1 month
Type: Drug
Group Labels: 1

Idebenone 900 mg/day

Name: Idebenone

Description: 2250 mg/day for 1 month
Type: Drug
Group Labels: 1

Idebenone 2250 mg/day

Name: Placebo

Description: Placebo - No idebenone
Type: Other
Group Labels: 1

placebo


Primary Outcomes

Description: To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)

Measure: Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)

Time: Up to 4 weeks from baseline

Secondary Outcomes

Description: To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration

Measure: Mean Change in Venous Lactate Concentration

Time: Up to 4 weeks from baseline

Description: To assess changes following 1 month treatment with 2 different doses of idebenone with that of placebo in fatigue as assessed by the Fatigue Severity Scale (FSS). Scale score minimum is 9 (least fatigue) and maximum is 63 (maximum fatigue). Scores of 36 or less indicate possibility that patient may not be suffering from fatigue, while scores 36 and over suggest suffering from fatigue

Measure: Mean Change in Score on the Fatigue Severity Scale (FSS)

Time: Baseline and Week 4

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 A3243G

Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

metal implant, claustrophobia) - Stroke like event within 2 months prior to baseline - Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline - Inadequate contraception use - Pregnancy and/or breast-feeding - Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine - Current abuse of drugs or alcohol - Participation in a trial of another investigational drug within the last month - Other factor that, in the investigator's opinion, excludes the patient from entering the study Inclusion Criteria: - Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss) - Cerebral lactate level equal to or greater than 5.0 i.u. at baseline - Patients at least 8 and < 65 years of age at baseline - Patients with a body weight > 37 kg/82 lbs at baseline - Stable co-medication/vitamins/supplements within 1 month prior to baseline - Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication - Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion Criteria: - Contraindication to MRS (e.g. --- A3243G ---

Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group. --- A3243G ---

The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). --- A3243G ---



HPO Nodes


HPO:
HP:0001941: Acidosis
Genes 483
NDUFS7 DLAT COQ8A EPG5 MYO5B COQ2 ST3GAL5 KYNU ND5 HLCS TRNS2 TAZ YARS2 TWNK RRM2B C12ORF65 IVD PREPL NDUFAF3 LIPT1 TRNL1 KCNJ11 PNPO ABCC8 NDUFA10 COX3 GFM2 OCRL NDUFV2 SLC25A4 TRNS1 GCDH SLC4A1 HADHA TRNT TACO1 PPA2 HSD17B10 SURF1 POLG TRNN NDUFV1 UQCRC2 TRMU COX10 TRNL2 TRNK MRPL3 MCCC1 LYRM7 SLC16A1 ND1 CYTB WNK1 RYR1 NDUFA6 NDUFS1 CLCNKB COX2 FASTKD2 INS TYMP EIF2AK3 RARS1 SCNN1A EHHADH PDX1 BCKDHA ATP5F1D SDHA NDUFS3 FBP1 PDSS1 NDUFB11 GLYCTK NDUFA11 ND3 HMGCL VPS33B PC DGUOK CTNS AIFM1 PDHB CYP11A1 ELAC2 ND1 TRNQ COX6B1 SLC25A26 LCT NDUFB8 DGUOK COX8A ND3 ACADS TMEM126B INS RMND1 NDUFS7 NDUFS2 TK2 ACSF3 NDUFS2 ACSF3 TRNS1 NDUFAF5 MMAA NDUFS2 COX2 LYRM4 INSR PCK1 IBA57 POLG2 COQ4 IVD AGK FBP1 MPC1 SLC25A42 WNK4 SLC25A4 TIMM50 DPYS OCRL TRMU SCO2 NDUFA2 LRPPRC SDHA PTPN22 AGXT MRPS22 ACAT1 NEUROG3 ND1 NDUFB8 NDUFS6 YARS2 PHKG2 TRNL1 NDUFA12 NDUFAF4 TRNL1 ND6 ECHS1 BTD NDUFV2 ETFA TIMM50 AUH ND2 SLC25A4 FN1 UQCC3 NDUFB3 HADHB DLD MTFMT BCS1L OGDH TUFM SCO2 TRMT5 MMACHC HMGCL CTNS AGK TSFM ALDH6A1 CARS2 TRNS1 MRPL44 PCCA NDUFS2 COX1 SURF1 ND5 NDUFAF6 TRNE COQ9 ACADVL ND4 WARS2 SDHA ATAD3A TRNQ HNF1A MMUT SUCLA2 COX10 COX1 COX15 NDUFA11 TWNK SLC19A3 UQCRQ RYR1 UQCRB MRPS16 PDHA1 FOXRED1 NDUFS1 NDUFAF2 SLC52A1 GCK PET100 CARS2 SYNJ1 SLC25A3 MRPS7 NDUFB9 G6PC FOXRED1 SERAC1 NDUFS7 GFER TRNV VIPAS39 COX14 ACAD9 KCNJ5 PUS1 PMPCB CA2 FARS2 GTPBP3 HNF4A UQCC2 NDUFAF1 SLC25A13 TRNN PHKG2 ND6 NDUFV1 USP18 BCS1L PUS1 ND6 TRNT TANGO2 TRNL1 PET100 CPT1A COX15 NDUFA10 TRNC TRNI TRNW TRNF MICOS13 NDUFA6 NDUFS1 DNAJC19 ACAT1 GALT NDUFAF4 NGLY1 SLC4A4 ND2 SLC2A2 MLYCD POLG SHOX NDUFAF1 BCKDHB NDUFAF3 CA5A INSR SLC25A3 SLC12A3 POLG PRDX1 ETFDH CAMKMT COA8 IL6 SCO2 TXN2 NAXE CLDN16 FH GK ND4 TRNT1 TACO1 SLC37A4 NADK2 POLG2 NDUFA9 TWNK PPM1B TRNF AARS2 GSS SCNN1G ATPAF2 SLC3A1 EPG5 MTO1 ISCU FBXL4 NDUFS4 ITPR3 MARS1 SUCLG1 NDUFA1 CAD NDUFS3 ACAD9 COX20 SLC4A1 MRPS34 TRNW NDUFAF2 TWNK OXCT1 KLHL3 FOXRED1 SLC25A19 HPD SURF1 HS6ST2 INVS NDUFS6 NDUFAF3 CYP11B2 TRNF NDUFV1 HTRA2 ADAMTS13 SLC5A1 NEUROG3 COA6 DARS2 KYNU TMEM126B LIAS GFM1 PLVAP CACNA1S NDUFS3 PCCB HSD3B2 C1QBP SCNN1B MDH2 PDHX POLG2 TIMMDC1 LDHA ALDOB PLPBP TRMT10C NDUFAF5 SLC25A19 POLG ST3GAL5 PAX4 MTFMT LARS1 WDR35 ITGA3 GCDH FDX2 COQ2 NDUFS8 ND1 TRNK NARS2 NDUFA13 COQ8A TRNL1 NDUFA9 NDUFS4 TARS2 HPD POLG DLD NOTCH2 PNPO SLC7A7 CYTB TRNV TK2 TRNP PDSS2 NDUFB10 TRNS1 NDUFAF5 CHCHD10 ACAT2 LIPT2 RNASEH1 POLG ATP6V0A4 ETHE1 RARS2 COA8 PDHA1 MCEE NDUFS4 ETHE1 ND5 NDUFB11 GYS2 TWNK LARS2 TRNW COX3 RRM2B SLC37A4 BCS1L TYMP JAG1 TMEM70 NDUFA4 TRNH NDUFA13 PHKA2 NDUFB9 NFU1 SCO1 NDUFA2 ATP6 PNPT1 TRNS2 TXN2 PNPLA8 EARS2 DNM1L NUBPL TRNK MCCC2 ISCA1 ALDOB TANGO2 MRPS14 HIBCH RRM2B MIPEP NDUFV2 NR3C2 ATP5F1E GATA3 NDUFS8 SFXN4 SDHAF1 ATP6V1B1 HADH CUL3 CPT1A BOLA3 ECHS1 STX3 PDSS2 GTPBP3 CYC1 BCS1L LIPT1 PDP1 SLC25A4 TRNW MMAB MPV17 NDUFB3 ACADM DBT AIFM1 SURF1 CLPB CYP11A1 NDUFAF6 BTD TPK1 POLG AGXT CHCHD10 NDUFA1 SDHD ETFB TRNK
Protein Mutations 0
SNP 0
HP:0001298: Encephalopathy
Genes 334
ACTL6B SLC19A3 GABRA1 TH RNASEH2C CACNA1B NDUFA6 SYNJ1 TRAK1 COG8 NDUFAF4 KYNU ND5 CLTC PNKP TCF4 TRNS2 ND2 TRAK1 SLC2A1 FGF12 KCNB1 CNTNAP2 NDUFAF1 PPP3CA MAPK10 CACNA1E TK2 PNPO SLC12A3 KCNQ5 COX3 SPTAN1 TP53 NAXE NDUFV2 BSCL2 RANBP2 TRNS1 GABRG2 NADK2 SLC1A2 MST1 GCDH TRNF DHDDS SLC6A9 KCNA2 GABRB3 SLC25A22 GRIN2B GNAO1 CHD2 ARHGEF9 FBXL4 KCNQ2 NDUFS4 SUCLG1 CAD ZNHIT3 NDUFS3 ACAD9 SLC19A3 LYRM7 SCN1B NEUROD2 PRNP TRNW CYTB CCDC88A SCN9A NDUFA6 DNM1 NDUFS1 KMT2E RANBP2 CLCNKB ACY1 DPM2 DENND5A ALG9 COX15 ITPA SLC35A1 SLC35A2 NDUFS6 GABRB2 TBCD HADH NDUFAF3 STAG1 ATP1A3 RNF13 TBCE GPT2 NDUFV1 ATP5F1D PARS2 CACNA1A SERPINI1 GLYCTK NDUFA11 ST3GAL3 NRXN1 KYNU NRXN1 TMEM126B LIAS CACNA1A ASNS ATP5F1A NDUFS3 COG8 ND1 TBCE PCCB UNC80 FCSK DNM1 ATP5F1A ARX HTRA1 SZT2 DGUOK MDH2 MDM2 TBC1D24 ND3 TBCK GABRB2 TIMMDC1 AP3B2 ADAM22 NTRK2 CPT2 GABRA5 TRIT1 NDUFAF5 KCNQ2 SLC25A22 SYNGAP1 NDUFS7 WDR45 NDUFS2 NUS1 ACSF3 SLC25A20 SCN1A SCN3A GABRB3 KCNA2 CHD2 SLC1A2 COX2 GCDH AARS1 PCK1 IBA57 COQ2 NDUFS8 COQ4 ND1 STAT2 TRNK EEF1A2 MPC1 SLC25A15 SLC13A5 KCNT2 ATP6V1A HCN1 DLD CACNA1B PIGP GRIN2D ROGDI PNPO ATAD1 CUX2 TRNV NDUFAF2 BSCL2 NDUFB10 UBA5 NAXD PHACTR1 LIPT2 GABRB1 NDUFS6 RNASEH2B ETHE1 CDKL5 NDUFAF4 TRNL1 CLCN4 GBA ACY1 AMACR PPP3CA TIMM50 HCN1 TCF4 NDUFB3 NDUFS4 ETHE1 NDUFB11 DLD SZT2 TUFM SH2D1A KCNT1 SLC22A5 GLUL GBA HMGCL TSFM BCS1L AP2M1 CNPY3 CARS2 KCNB1 FADD SYNGAP1 STXBP1 DNM1 SLC25A13 CLP1 PCCA TMEM70 HNRNPU PACS2 FRRS1L CHEK2 NECAP1 D2HGDH MEF2C EEF1A2 SLC6A1 YWHAG NBAS GPR35 COQ9 AP3B2 DHDDS PNPT1 TRNQ SLC25A12 UBA5 CNKSR2 FGF12 GUF1 SIK1 DNM1L NUBPL SUCLA2 GLS NUS1 ARHGEF9 COX1 ARV1 ARV1 NDUFA11 TBC1D24 PLCB1 DOCK7 HIBCH GABRG2 NDUFAF2 SLC25A15 WWOX CARS2 GCSH SYNJ1 NDUFV2 SCN8A ATP6V1A SLC22A5 SLC13A5 NDUFB9 HADH STXBP1 CPT1A TRAPPC12 BOLA3 XIAP FOXRED1 SIK1 SERAC1 NDUFS7 NAGS PIGA PARS2 CYC1 ACAD9 FADD CYFIP2 AARS1 TREX1 PMPCB MECP2 NTRK2 NDUFAF1 TWNK TGFB1 ND6 GRIN1 SLC25A1 SCN2A NDUFB3 CHD2 GRIN2D SCN3A UGT1A1 CLPB NADK2 GLDC CACNA2D2 SCN8A KCNA2 TSEN54 CPLX1 SCN1A NDUFA1 AMT NECAP1 WWOX FBLN1 GABBR2 CDKN2A TRNC TRNK CUX2 GABRA2 CYFIP2
Protein Mutations 1
A3243G
SNP 0