Liver and Metabolic Effects of Insulin Pump Therapy in Diabetics Type 2 With Non-alcoholic Hepatic Steatosis

Type 2 Diabetes (T2D) Clinical Trial

— STEATO-POMPE  

Official title:

Liver and Metabolic Effects of Insulin Pump Therapy in a Population of Type 2 Diabetics With Non-alcoholic Hepatic Steatosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04270656
• Other study ID #: RC19_0449
• Status: Recruiting
• Phase: N/A
• Start date: February 5, 2021
• Est. completion date: April 5, 2023

Study information

• Verified date: March 2021
• Source: Nantes University Hospital
• Contact: Matthieu Pichelin
• Phone: 02.53.48.27.06
• Email: matthieu.pichelin[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prevalence of fatty liver disease (NAFLD: Non-Alcoholic Fatty Liver Disease or to a more severe degree NASH: Non-Alcoholic SteatoHepatitis) reached 40-70% in subjects with type 2 diabetes (T2D). NAFLD can be easily detected by performing a hepatic ultrasonography. The presence of a NAFLD is positively correlated with the severity of insulin resistance and dysglycemia in this population. The presence of NAFLD worsens the prognosis of T2D with an increased cardiovascular risk. This hepatic impairment would also increase the risk of microvascular complications, especially nephropathy. Conversely, T2D increases the risk of transition from NAFLD to NASH and then to hepatic fibrosis and its related complications (cirrhosis, hepatocellular carcinoma). The risk of progression of liver steatosis to fibrosis is also more important as diabetes and insulin resistance are more severe.

In addition to diabetes and insulin resistance, other risk factors are associated with more severe liver damage such as changes in microbiota. Indeed, it has already been described a smaller amount of bacteroides in the microbiota of subjects with T2D and the most severe hepatic impairment. The treatment of NAFLD/NASH is poorly codified without approved drugs in this indication, while many phase 3 trials with candidate drugs are undergoing. Life-style measures (physical activity and low carbohydrate/calorie diet) can limit the progression from NAFLD to more severe liver fibrosis. Some bariatric surgery studies have also shown good results in this situation. Pharmacological interventions are also reported with proven efficacy of pioglitazone, vitamin E and orlistat.

The OPT2MISE study has recently shown the superiority of insulin pump (or continuous sub-cutaneous insulin infusion: CSII) compared to multiple daily insulin injections (MDI) to improve glycemic control in a population of patients with T2D in failure of well-titrated MDI. In addition, treatment with CSII showed a 45% decrease in insulin resistance (assessed by HOMA-IR) in a population of newly diagnosed T2D.

In light of these data, investigators hypothesize that the introduction of insulin pump treatment in a population of subjects with T2D and NAFLD, by improving insulin sensitivity, could reduce fatty liver content compared to standard MDI treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: April 5, 2023
• Est. primary completion date: April 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 37 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male / female 35/70 years (including ranges) with T2D = 1 year

• Benefiting from the indication of use of the free Freestyle glucose meter

• Treatment with multi-injection insulin therapy comprising a daily injection of basal insulin (Glargine U100, Glargine U300, Degludec) and at least 2 daily injections of an insulin analogue (lispro, aspart or glulisine) +/- metformin, dipeptidyl peptidase-4 (DPP4) and/or sodium-glucose cotransporter type 2 (SGLT2) at a dose stable for at least 3 months.

• For women of childbearing age, oestro-progestative pill, IUD, implant.

• 11% = HbA1c = 6.5%

• Presence of hepatic steatosis according to the ultrasonography

• Absence of chronic alcoholic intoxication

• Absence of chronic viral hepatitis or other chronic liver diseases (eg hemochromatosis ...)

Exclusion Criteria:

• Type 1 diabetes

• Contraindication to pump treatment

• Treatment with anti-diabetics or other than metformin, dipeptidyl peptidase-4 (DPP4) and/or sodium-glucose cotransporter type 2 (SGLT2)

• Treatment with basal inulin of Levemir

• Contraindication to performing MRI

• Chronic alcohol abuse (after alcohol consumption> 20g / day in men and> 10g / day in women) according to the medical examination

• Chronic viral hepatitis based on HBV and HCV serology results

• Hemochromatosis according to the martial assessment

• Other toxic or drug hepatitis

• Severe hepatic pathology: hepatic cirrhosis, hepatocellular carcinoma

• Severe renal insufficiency (MDRD <30 ml / min)

• Severe and progressive cardiovascular pathology

• Treatment (permanent or intermittent) with glucocorticoids

• Treatment known to improve hepatic steatosis (glitazone, vitamin E, orlistat)

• history or bariatric surgery project for the duration of the study

• Drug treatment likely to cause hepatic steatosis (amiodarone, carbamazepine, tamoxifen, valproate, clozapine, anti-retroviral drugs) unless the dose has been stable for = 3 months

• Guardianship, curatorship or safeguard of justice

Related Conditions & MeSH terms

• Fatty Liver
• Type 2 Diabetes (T2D)

Intervention

Procedure:
• Insulin pump therapy
5-day hospitalization in case of randomization in the insulin pump group (insulin pump establishing in according to the recommendations of the HAS)
• Multi-injection treatment ( MDI ).
Corresponds to an outpatient visit if the patient is randomized into the multi-injection group

Locations

Country	Name	City	State
France	CHU	Angers
France	CHU	Caen
France	CHU	Dijon
France	CHU	La Rochette
France	Hospices Civils	Lyon
France	Nantes UH	Nantes
France	CHU	Poitiers
France	CHU de Rennes	Rennes
France	CHU	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variation of hepatic steatosis, between the insulin pump therapy (CSII) vs Multi injection treatement (MDI) groups.	Change of fatty liver by MRI quantification	6 months
Secondary	In the CSII group : avantage of an insulin pump treatment on the fatty liver between inclusion and the 6th month,	Variation of hepatic steatosis (MRI quantization by gradient echo sequences & centralized reading	6 months
Secondary	In the CSII group : avantage of an insulin pump treatment on the fatty liver (quantified by MRI), between inclusion and the 12th month,	Variation of hepatic steatosis (MRI quantization by gradient echo sequences & centralized reading	12 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months, on hepatic biological parameters and non-invasive biomarkers of fatty liver (FLI) and of fibrosis of the liver (FIB-4 and NAFLD Score),	Liver fonction (AST ; ALAT ; GGT ; PAL ; Ferritin) Test-fibrosis score criteria (FIB- 4 and NAFLD Score) ; FLI	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity	dosage of plasma adiponectin	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity	calculation of the modified HOMA-IR index (peptide C, blood sugar),	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on glycemic balance	HbA1c dosages	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on the total daily insulin dose	daily insulin dose record	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	total cholesterol	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	LDL-cholesterol	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	HDL-cholesterol	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	triglycerides (TG)	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	fatty-free acids	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition	ApoB,	6 months
Secondary	Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on CRPus	Ultra-sensitive C-reactive protein (CRPus)	6 months
Secondary	Evaluation of quality of life	DTSQ	6 months
Secondary	Evaluation of quality of life	SF36	6 months
Secondary	Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:	Reporting by patient of all severe hypoglycemia during the study	6 months
Secondary	Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:	Reporting by the patient of all episode of ketoacidosis during the study	6 months
Secondary	Calculation of the sensitivity values of the FLI for the detection of fatty liver in this population,	quantification of hepatic MRI as Gold Standard.	6 months
Secondary	Calculation of the specificity values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.	quantification of hepatic MRI as Gold Standard.	6 months
Secondary	Calculation of the positive predictive values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.	quantification of hepatic MRI as Gold Standard.	6 months
Secondary	Calculation negative predictive values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.	quantification of hepatic MRI as Gold Standard.	6 months