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Report for Clinical Trial NCT01045525

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Prospective Randomized Study Comparing the Effect of Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only on Glycemia in Patients With Dysmetabolic Liversiderosis

Insulin resistance-associated hepatic iron overload (IR-HIO), also defined as dysmetabolic iron overload syndrome or dysmetabolic liversiderosis, is a common cause or iron overload in France, mainly in middle-age patients with increased serum ferritin levels associated with normal serum transferrin saturation, and normal serum iron concentration in the absence of other known cause of increased serum ferritin levels. Treatment includes a combination of dietary measures and physical activity to correct metabolic disorders. Phlebotomies seem to be beneficial when serum ferritin level is high. This study aims at comparing the effect of iron depletion (by phlebotomy) plus lifestyle and diet advices versus lifestyle and diet advices alone on blood glucose level and insulin sensitivity in subjects with IR-HIO in order to assess the benefits of phlebotomies on the reduction of risk of diabetes and cardiovascular associated complications.

NCT01045525 Liver Cirrhosis Iron Overload
MeSH: Liver Cirrhosis Iron Overload
HPO: Cirrhosis Hepatic fibrosis

2 Interventions

Name: Phlebotomy

Description: From 300 to 400mL for women; From 350 to 450mL for men

Type: Procedure

Phlebot Phlebotomy + lifestyle and diet advices

Name: Lifestyle and diet advices

Description: 2 Booklets with Dietary and physical activity advices

Type: Behavioral

Lifestyle and diet advices


Primary Outcomes

Measure: Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)

Time: 12 months

Secondary Outcomes

Measure: Rate of Body mass index > 25 kg/m²

Time: 12 months

Measure: Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive treatment

Time: 12 months

Measure: Rate of abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women)

Time: 12 months

Measure: Rate of fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment

Time: 12 months

Measure: Rate of fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment

Time: 12 months

Measure: Rate of fasting glycemia ≥ 5.6 mmol/L

Time: 12 months

Measure: HbA1c value

Time: 12 months

Measure: Quality of life estimated with SF36 form and tolerance to treatment

Time: 12 months

Measure: Insulinoresistance indexes calculated at T0 and T30 min of Oral Glucose Tolerance Test (OGTT)

Time: 12 months

Measure: Biological markers: CRP, hyaluronic acid, fibrometer

Time: 12 months

Description: Two dimensional (2D) speckle tracking echocardiography (STE)

Measure: myocardial deformation

Time: 12 months

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 C282Y

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y ---

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y --- --- C282Y ---



HPO Nodes


HPO:
Cirrhosis
Genes 164
TTC37 TMEM67 GDF2 ATP7B F5 MPV17 HJV IGF2R SLC40A1 POLG ARHGAP31 CCDC115 ATP8B1 BSCL2 HFE TREX1 TTC37 JAK2 BCS1L TFR2 AGPAT2 ACVRL1 TERC FOS POU2AF1 APOE TYMP SLC30A10 BSCL2 CTC1 NOP10 UROD CAV1 INPP5E NOTCH1 TP53 ENG NHP2 FECH DOCK6 LIPA KRT8 SKIV2L RPGRIP1L SMAD4 PPARG LIPA TFAM NGLY1 TERC RPGRIP1L AP1S1 MARS1 DCDC2 SKIV2L RTEL1 GPC1 PARN BSCL2 ALMS1 TERT KRT18 SERPINA1 GBA TNFSF15 HSD3B7 ATP7B ABCB11 SFTPC GALT GLRX5 USB1 PEX1 HFE ITCH TINF2 ALDOB IL21R AKR1D1 F5 GPR35 SLC25A13 ENG TMEM67 CYP7B1 MPI APC TERC TALDO1 CTNNB1 TERT SLC7A7 NR1H4 GBE1 HSD3B7 JAG1 CASP8 HFE BMP2 HAMP CC2D2A EOGT FARSB COG4 TERT SCARB2 ABCB4 CAVIN1 SMPD1 MUC5B RBPJ TALDO1 PIGA AXIN1 TCF4 NPM1 COG4 WRAP53 AP1B1 IL12A LBR JAK2 ASS1 TINF2 DKC1 PHKG2 NPHP3 TRMT5 DKC1 FAH SPIB PHKG2 AGPAT2 DGUOK HBB MST1 ATP6AP1 COG6 ABHD5 PHKA2 SLC40A1 PPARG PDGFRL ACVRL1 DLL4 SLC30A10 IL12RB1 AMACR KRT18 IRF5 SFTPA2 IFT43 MET PIK3CA TREX1 MMEL1 KRT8 PPARG RRM2B TERT NHP2 CC2D2A POLG TNPO3
Hepatic fibrosis
Genes 140
CSPP1 TTC37 DYNC2H1 BBS9 TMEM67 MET IFT122 DZIP1L TMEM67 SLC40A1 WDPCP ARHGAP31 ABCB4 TTC37 GPD1 WDR35 NPHP3 POU2AF1 BBS10 SDCCAG8 C8ORF37 IQCB1 DLL4 PLIN1 BBS1 WDPCP SLC25A13 CEP290 NOP10 INPP5E NOTCH1 SCYL1 PTRH2 DOCK6 TMEM67 BBS7 CC2D2A SKIV2L RPGRIP1L DCDC2 TCTN2 LIPA TMEM67 IFT172 PMM2 NPHP3 RPGRIP1L CTNNB1 AP1S1 PKHD1 WDR35 GPC1 TTC8 NEK1 B9D1 PMM2 TNFSF15 RPGRIP1 NPHP1 BBIP1 INSR FADD INVS OFD1 CCDC28B PEX1 MKS1 PNPLA6 NEK8 CC2D2A LZTFL1 INPP5E RPGRIP1L ANKS6 GPR35 NPHP4 TMEM67 CEP290 MPI TMEM231 IFT80 MPI ARL6 AGL WDR60 CEP55 ASL ALG9 CC2D2A EOGT BBS2 MKKS IFT27 GLIS3 BBS5 INSR CEP290 TRIM32 ABCD3 TRAF3IP1 TMEM107 SDCCAG8 BBS1 DOLK MKS1 RBPJ TALDO1 TCF4 IL12A NPHP1 NHP2 WDR19 TMEM67 HJV HAMP TRAF3IP1 CYP7B1 NPHP3 SPIB PHKG2 IFT140 DGUOK MST1 B9D2 PHKA2 SLC40A1 WDR34 BBS4 PKHD1 TMEM216 SCYL1 DLL4 CEP164 IL12RB1 IRF5 MMEL1 BBS12 IFT172 CC2D2A TNPO3