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Report for Clinical Trial NCT00887562
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
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.
Name: Idebenone
Description: 900 mg/day for 1 monthType: Drug
Idebenone 900 mg/day
Name: Idebenone
Description: 2250 mg/day for 1 monthType: Drug
Idebenone 2250 mg/day
Name: Placebo
Description: Placebo - No idebenoneType: Other
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:Acidosis
Genes 479
CYP11A1 AIFM1 ND5 GYS2 CLPB SLC16A1 GFM2 COX15 ND1 STX3 LYRM4 TRNS1 TRNL1 COQ2 MTFMT MCCC2 NDUFB9 TYMP NDUFV2 GCK INS NDUFS6 NDUFAF4 COX2 SURF1 NUBPL COQ2 NDUFB10 TRNQ SLC25A4 SLC19A3 HMGCL BCKDHA CA2 SURF1 UQCRB KCNJ5 MTO1 MARS1 TRNP TRNT OCRL NAXE VIPAS39 HTRA2 BCS1L TRMT10C DNM1L NDUFAF5 COX6B1 NDUFV2 COX3 ND2 SDHA LARS2 EHHADH PPM1B PLPBP GCDH TRMU PDX1 SURF1 COX8A MMAB CAMKMT NDUFA11 SLC4A4 MLYCD ALDH6A1 SDHD TRNF PNPLA8 NDUFA9 NFU1 NDUFS2 COX14 ATPAF2 NDUFS7 SERAC1 AGXT LIPT2 HLCS MPC1 ACAT1 BCKDHB SCNN1G AARS2 ELAC2 NDUFS2 CYTB NDUFS1 PET100 RYR1 COX20 ST3GAL5 NDUFAF6 TRMT5 NDUFA1 RARS1 PHKG2 AIFM1 HSD17B10 NDUFAF2 SURF1 NDUFS1 TSFM ACSF3 MRPS7 AUH COX1 MIPEP ISCU TRNS1 ND5 SLC25A3 ECHS1 POLG ACADS POLG TRNL2 PDHX SLC7A7 HADHA C12ORF65 ATP5F1D TWNK UQCRQ COA8 TRNH BCS1L VPS33B NDUFA10 FOXRED1 NDUFAF3 BCS1L NDUFV1 TRNK TRNL1 ND4 NGLY1 SDHA POLG ND2 CPT1A RMND1 NDUFA2 NDUFS1 HNF1A GLYCTK USP18 AGK MRPL3 TACO1 MRPS22 ND1 NDUFS4 ACAD9 ATAD3A TK2 ADAMTS13 TAZ COQ9 FASTKD2 ETFB NDUFA6 NDUFAF5 TRNS1 NDUFB8 CARS2 NDUFA6 CAD GK ALDOB IVD SDHAF1 NDUFB11 PDSS1 COX15 POLG HPD TRNL1 IL6 COX1 INSR TK2 NDUFS6 TRNC NDUFA12 ATP6V0A4 NDUFA13 SLC5A1 ISCA1 NDUFS3 NDUFB9 NDUFB3 TRNW COX3 LIAS GFER PDSS2 KYNU PDHB TIMMDC1 INVS ITGA3 BCS1L TWNK COX2 SCO1 SLC4A1 MTFMT HIBCH TPK1 FOXRED1 PDHA1 PHKG2 PAX4 COQ8A RRM2B ACSF3 SLC25A42 GTPBP3 COX10 TMEM126B ND5 TARS2 COX10 CUL3 NDUFAF1 WARS2 FOXRED1 TRNK ATP6 CLCNKB NDUFAF2 SFXN4 SLC25A13 NEUROG3 SLC25A4 ETHE1 TRNF CHCHD10 DLD PRDX1 NDUFA1 YARS2 EPG5 MPV17 NDUFB3 NDUFA4 POLG TRNW COA8 ECHS1 ND6 HPD HSD3B2 ACAD9 PUS1 TRNV TMEM70 ND4 DBT NDUFAF3 MCCC1 ACADM NDUFS3 TRNT ITPR3 ETFA TYMP TRMU TACO1 CPT1A SLC37A4 FBP1 PCK1 TIMM50 NDUFS4 IBA57 TWNK TRNQ ATP6V1B1 NADK2 TRNN ABCC8 TRNN ND6 CA5A FN1 NDUFS7 SUCLG1 SCNN1B CACNA1S GATA3 LYRM7 C1QBP EPG5 LARS1 MRPS14 PTPN22 DLAT TRNK LRPPRC MCEE TRNV TWNK KLHL3 WNK4 CTNS PCCB NDUFAF4 LCT SLC4A1 AGK ALDOB SLC25A26 NOTCH2 ATP5F1E JAG1 TRNW MRPS16 COQ4 FBXL4 BTD CLDN16 BTD NDUFS2 NEUROG3 PLVAP BOLA3 PUS1 MICOS13 SLC25A4 SCNN1A UQCC3 ETHE1 ACAT1 UQCRC2 PDHA1 TIMM50 POLG SLC52A1 PREPL OXCT1 SLC25A19 CYP11B2 PDSS2 NDUFV1 ND6 SLC37A4 DARS2 KYNU SLC2A2 RNASEH1 FARS2 NDUFA13 TRNF NDUFB11 EARS2 EIF2AK3 DGUOK NDUFAF3 NDUFA11 ACADVL HMGCL DLD NDUFA2 RYR1 TRNS2 WDR35 RARS2 ND3 TRNL1 POLG2 NDUFS7 RRM2B MRPS34 PDP1 TWNK PNPO MYO5B CYC1 MMAA NDUFAF6 TRNW SLC25A4 TRNS2 TXN2 GSS TXN2 LDHA NDUFA10 G6PC NDUFV2 LIPT1 NDUFAF5 CARS2 NARS2 NDUFV1 NDUFAF1 GALT MDH2 ACAT2 TRNS1 TRNE TRNL1 POLG2 NDUFS3 OGDH PPA2 DPYS AGXT ND1 LIPT1 NDUFS8 FDX2 MRPL44 INS TRNI TMEM126B SLC12A3 SHOX POLG DNAJC19 ND1 HNF4A SCO2 KCNJ11 SUCLA2 COQ8A PC OCRL NDUFA9 FH SCO2 CYP11A1 HADH TANGO2 POLG2 SDHA PNPT1 TRNK SLC25A19 SLC3A1 WNK1 ETFDH SCO2 NDUFB8 TUFM NR3C2 ND3 ST3GAL5 COA6 DGUOK MMUT PET100 CHCHD10 CTNS HADHB PHKA2 YARS2 UQCC2 SYNJ1 GFM1 PCCA PNPO NDUFS2 TRNT1 SLC25A3 PMPCB HS6ST2 MMACHC IVD NDUFS4 FBP1 GCDH RRM2B NDUFS8 hr>Encephalopathy
Genes 332
ACY1 SCN9A KCNQ2 RANBP2 SIK1 DHDDS NDUFA1 CLPB WDR45 NDUFB3 SCN8A CUX2 SCN1A SLC35A1 SLC6A1 ND1 KCNA2 SLC25A15 ACAD9 TRNS1 KCNB1 PARS2 TSEN54 TMEM70 NDUFV2 GABRB3 UBA5 SLC2A1 BSCL2 SLC25A13 CLCN4 SCN3A GABRA2 NDUFS6 NDUFAF4 COX2 CPT1A SCN1A PCK1 NUBPL COQ2 TIMM50 NDUFB10 FGF12 YWHAG IBA57 TGFB1 TRNQ GRIN1 SLC25A20 NADK2 HMGCL UBA5 CACNA2D2 NECAP1 DOCK7 TRIT1 ND6 NBAS GABBR2 CDKN2A SCN3A SUCLG1 NAXE LYRM7 TRAK1 DNM1L KCNQ5 NDUFAF5 TREX1 TRNK NAXD COX15 DENND5A CHEK2 TBC1D24 GABRG2 TRNV NDUFV2 COX3 DNM1 GABRB3 SLC25A12 GLS GCDH GPR35 PCCB NADK2 NDUFA11 ATP5F1A CACNA1E NDUFAF4 CYFIP2 GRIN2D GBA UGT1A1 ALG9 DNM1 NUS1 RNASEH2C MDM2 COG8 TRNW NRXN1 COQ4 FBXL4 RANBP2 SCN1B PARS2 NDUFS2 GNAO1 SLC22A5 NDUFS7 KCNT1 SERAC1 TBC1D24 BOLA3 LIPT2 WWOX MPC1 GBA PIGP HCN1 CYTB CCDC88A PNKP KMT2E PPP3CA GRIN2D SLC1A2 ETHE1 SLC25A22 TBCK ROGDI BSCL2 STXBP1 TCF4 SLC22A5 NTRK2 SLC19A3 AP2M1 ATP6V1A KCNT2 AP3B2 MST1 COG8 NDUFV1 STXBP1 SLC25A22 TSFM KYNU GRIN2B COX1 HADH ARV1 ATAD1 CYFIP2 CDKL5 TRNF NDUFB11 GABRG2 GPT2 NDUFA11 ATP1A3 TWNK NAGS TRAPPC12 SLC13A5 DLD CPT2 TK2 ATP5F1D CACNA1B ATP5F1A AARS1 RNF13 TRNS2 FCSK FADD PRNP ASNS PHACTR1 NDUFS7 DHDDS AP3B2 ITPA SLC19A3 NDUFAF3 EEF1A2 ARX BCS1L CACNA1A TRNK SLC25A15 PNPO ARV1 ND2 CYC1 NDUFS1 PLCB1 GLYCTK ACY1 CACNA1B XIAP ARHGEF9 NDUFAF2 ND1 NDUFS4 ACAD9 NEUROD2 ADAM22 SLC13A5 COQ9 SLC25A1 PACS2 SZT2 CHD2 NDUFA6 CLP1 CARS2 CARS2 FADD MEF2C NDUFA6 CAD NDUFAF1 GCSH AARS1 TRAK1 MDH2 SYNGAP1 CHD2 HCN1 CACNA1A NDUFS3 SERPINI1 TRNL1 WWOX SCN8A NDUFS8 MECP2 GABRB2 GUF1 KCNA2 ST3GAL3 NDUFS6 SH2D1A TRNC SLC12A3 MAPK10 GLUL SPTAN1 D2HGDH ARHGEF9 SUCLA2 GABRA5 PPP3CA NDUFS3 NDUFB9 ZNHIT3 NDUFB3 CPLX1 STAT2 GABRB1 SLC6A9 KCNQ2 HADH LIAS GABRB2 KYNU PIGA TCF4 PNPT1 TIMMDC1 NUS1 KCNA2 AMT SZT2 FGF12 HNRNPU TBCE NECAP1 HIBCH TUFM FOXRED1 EEF1A2 CUX2 ND3 CNPY3 ACTL6B CNKSR2 ACSF3 DGUOK UNC80 TBCE NTRK2 NRXN1 TMEM126B ND5 TH CNTNAP2 SYNJ1 NDUFAF1 PCCA PNPO KCNB1 ATP6V1A SYNGAP1 AMACR CLCNKB NDUFAF2 SIK1 FRRS1L TP53 PMPCB CLTC DNM1 SLC1A2 DPM2 GLDC HTRA1 TBCD GABRA1 NDUFS4 RNASEH2B GCDH SLC35A2 ETHE1 SCN2A CHD2 SYNJ1 DLD hr>Lactic acidosis
Genes 221
NDUFA1 YARS2 MPV17 NDUFB3 COA8 ND1 ACAD9 LYRM4 TRNS1 PUS1 COQ2 TMEM70 ND4 TYMP NDUFV2 DBT TRNT TYMP TRMU NDUFS6 COX2 TACO1 SLC37A4 FBP1 PCK1 NUBPL COQ2 NDUFB10 IBA57 TRNQ SLC25A4 TRNQ NADK2 BCKDHA TRNN ND6 SURF1 CA5A MTO1 SUCLG1 TRNT NAXE BCS1L TRMT10C LYRM7 DNM1L LARS1 NDUFAF5 COX6B1 MRPS14 DLAT LRPPRC TRNV NDUFV2 COX3 SDHA LARS2 PPM1B TRMU COX8A PCCB CAMKMT NDUFA11 NDUFAF4 AGK MLYCD SLC25A26 ATP5F1E SDHD TRNW MRPS16 FBXL4 TRNF PNPLA8 NFU1 NDUFS2 COX14 ATPAF2 SERAC1 BOLA3 LIPT2 MPC1 BCKDHB AARS2 ELAC2 CYTB PUS1 PET100 MICOS13 UQCC3 ETHE1 COX20 NDUFAF6 PHKG2 PREPL SLC25A19 HSD17B10 PDSS2 NDUFV1 ND6 NDUFS1 SLC37A4 TSFM MRPS7 COX1 MIPEP ISCU FARS2 ND5 SLC25A3 TRNF NDUFB11 EARS2 NDUFAF3 NDUFA11 POLG PDHX HADHA DLD ATP5F1D COA8 TRNH BCS1L TRNS2 NDUFA10 NDUFS7 FOXRED1 RRM2B MRPS34 NDUFAF3 BCS1L PDP1 TRNK TRNL1 ND2 CYC1 RMND1 NDUFS1 USP18 AGK SLC25A4 ND1 NDUFS4 TRNS2 ACAD9 G6PC TAZ COQ9 FASTKD2 NDUFA6 TRNS1 LIPT1 NDUFAF5 TRNS1 TRNE ALDOB SDHAF1 NDUFS3 COX15 OGDH TRNL1 NDUFS8 COX1 TK2 NDUFS6 TRNC POLG ND1 SUCLA2 NDUFS3 NDUFB9 COQ8A PC NDUFB3 FH TRNW SCO2 COX3 HADH LIAS GFER TANGO2 SDHA PDHB TIMMDC1 SLC3A1 BCS1L COX2 SCO1 TPK1 TUFM FOXRED1 PDHA1 PHKG2 COQ8A ND3 COA6 DGUOK SLC25A42 GTPBP3 COX10 HADHB TMEM126B ND5 PHKA2 COX10 YARS2 NDUFAF1 PCCA WARS2 NDUFS2 TRNT1 NDUFAF2 SLC25A3 SFXN4 SLC25A13 SLC25A4 NDUFS4 RRM2B ETHE1 DLD hr>Metabolic acidosis
Genes 101
PDHX ACADVL HMGCL DLD RYR1 HPD STX3 VPS33B MCCC2 BCS1L NDUFV1 MCCC1 ACADM PNPO NDUFAF4 MYO5B FBP1 MMAA IBA57 NDUFA2 GLYCTK HMGCL MRPS22 UQCRB KCNJ5 CA5A GSS MTO1 SCNN1B CACNA1S VIPAS39 C1QBP NDUFA6 NDUFAF1 GK GALT MCEE ALDOB IVD EHHADH NDUFB11 PLPBP GCDH OGDH CTNS PCCB PPA2 MMAB DPYS HPD AGXT LCT SLC4A1 MLYCD ALDH6A1 ALDOB BTD NDUFA9 HNF4A SLC5A1 BTD NDUFS7 AGXT PLVAP FH HLCS SCNN1G TANGO2 KYNU POLG2 SLC25A19 INVS WNK1 SCNN1A RYR1 HIBCH NDUFB8 TUFM NR3C2 ACAT1 UQCRC2 SLC52A1 MMUT HSD17B10 CYP11B2 SLC37A4 CUL3 UQCC2 GFM1 KYNU AUH PCCA PNPO SLC25A3 SLC25A3 MMACHC IVD ACADS FBP1 GCDH PRDX1 hr>