Anti-inflammatory Status in DM2 Treated Patients (INF-DM2-Ther)

Comparison of Anti-inflammatory Status Linked to Atherosclerosis Formation/Progression Among Diabetes Mellitus Type 2 Patients Under Combined Pharmacological Therapy

Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear. Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin / alogliptin Oral Product; Drug: Metformin / Pioglitazone Pill; Drug: triple therapy

Detailed Description

Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear . Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • ASP Catanzaro
    • Contact: Antonio Guerra, MD; Phone Number: 3398199190; Email: guerra.antonio@simg.it
    • Sub-Investigator: Antonio Scuteri, MD
    • Sub-Investigator: Giacomo Leuzzi, MD
    • Sub-Investigator: Giuseppe Giuliano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DMT2 patients were enrolled in presence of

  1. Age >35 and <75 years old
  2. Uncontrolled diabetes during treatment (glycosylated hemoglobin (HbA1c) > 75 mmol/mol )
  3. Combined therapy at least by 6 months.

Exclusion Criteria:

1. HbA1c < 75 mmol/mol (9%);
2. History of drug abuse or alcohol abuse, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year;
3. Estimated glomerular filtration rate (GFR) <30 ml/min (according to MDRD formula)
4. .Liver Failure
5. Recent history of Heart stroke, systemic infections, dehydration, lactic acidosis
6. Heart failure (NYHA I - IV)
7. Active bladder cancer or history of bladder cancer
8. macroscopic haematuria of unidentified nature
9. hypersensitivity to drug used (metformin, alogliptin, pioglitazone)
10. breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: metformin/alogliptin; metformin/alogliptin (850 mg/12.5 mg or 1000 mg/12.5 mg every 12 hours) for 12 months	Drug: Metformin / alogliptin Oral Product; 850 or 1000 mg/ 12.5 mg every 12 hours for 12 months
ACTIVE_COMPARATOR: metformin/pioglitazone; metformin/pioglitazone (850 mg/15 mg every 12 hours) for 12 months	Drug: Metformin / Pioglitazone Pill; (850 mg/15 mg every 12 hours) for 12 months
ACTIVE_COMPARATOR: triple therapy; metformin/pioglitazone (850 mg/15 mg every 12 hours)+alogliptin (12.5 mg every 12 hours) for 12 months	Drug: Metformin / alogliptin Oral Product; 850 or 1000 mg/ 12.5 mg every 12 hours for 12 months; Drug: Metformin / Pioglitazone Pill; (850 mg/15 mg every 12 hours) for 12 months; Drug: triple therapy; Metformin / Alogliptin/ Pioglitazone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammatory miRNA	Change from Baseline at 12 months	12 months
side effects	statistically significant difference (P<0.05) in the development of side effects between the groups, recorded using the Naranjo adverse drug reactions scale	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body weight	effects of each treatment on body mass index (kg/m^2) (as indirect indexes of systemic inflammation and visceral adiposity).	12 months
Waist values	effects of each treatment on waist values (cm) (as indirect indexes of systemic inflammation and visceral adiposity).	12 months
drug interaction	statistically significant difference (P<0.05) in the development of drug-drug interactions, recorded using the DIPS scale	12 months
Fasting blood glucose	effects of each treatment on fasting blood glucose (mg/dL) (as indexes of glucose metabolism);	12 months
HbA1c levels	effects of each treatment on HbA1c levels (percent) (as indexes of glucose metabolism);	12 months
liver function	alanine aminotransferase, aspartate aminotransferase, gamma glutamyl-transpeptidase levels, and total bilirubin levels (expressed as mg/dL) (as indexes of liver function).	12 months
cell count	effects of each treatment on white blood cell count expressed as cell/mm3 (as direct index of systemic inflammation)	12 months
lipid metabolism/atheroscelorisis	total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides levels (expressed as mg/dL) (as direct indexes of lipid metabolism and atheroscelorisis).	12 months

Collaborators and Investigators

• Sponsor: University of Catanzaro

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2020
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ANTICIPATED): June 20, 2021

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (ACTUAL): May 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 11, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Pioglitazone; Alogliptin
• Other Study ID Numbers: Inflammation-DM2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No