Rapid Effects Linagliptin on Monocyte Polarization and Endothelial Progenitor Cells in Type 2 Diabetes

NCT01617824 | Completed Phase 4

• 1 other identifier: 2588P
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes mellitus is characterized by chronic low grade inflammation, which is worsened by the co-existence of renal failure. One key aspect of chronic inflammatory diseases is the alteration in the polarization profile of circulating monocyte-macrophage cells. Namely, monocytes-macrophages can exist in a pro-inflammatory (M1) polarized form or an anti-inflammatory (M2) polarized state. Alterations in the M1/M2 balance is thought to contribute to inflammation within atherosclerotic lesions and visceral adipose tissue which, in turn, can worsen cardiovascular disease and metabolic features in type 2 diabetic patients. M1 and M2 are regulated by a complex interplay of soluble signaling molecules, many of which are substrate of the enzyme DPP-4 (dipeptidyl peptidase-4). Therefore, inhibition of DPP-4 can affect the M1/M2 polarization balance. In this clinical trial, the investigators will test whether the DPP-4 inhibitor Linagliptin, compared to placebo, modifies the M1/M2 balance in type 2 diabetic patients with and without chronic renal failure. In addition, we will test whether DPP-4 inhibition with Linagliptin acutely affects endothelial progenitor cells (EPCs), which are vasculoprotective cells implicated in the pathobiology of diabetic complications.

Conditions

Type 2 Diabetes; Chronic Renal Failure

Keywords

Diabetes; Kidney; Inflammation; Metabolism

Outcome Measures

Primary Outcomes (1)

• M1/M2 polarization balance

  Evaluate whether 4-days Linagliptin treatment, compared to placebo, significantly reduces the M1/M2 ratio in type 2 diabetic patients. In this cross-over design trial, Linagliptin and placebo will be administered once daily for 4 consecutive days to 30 type 2 diabetic patients with or without renal failure with a 2 week washout period in between.

  day 5

Secondary Outcomes (2)

• Cytokine and chemokine concentrations

  day 5

• Endothelial progenitor cell levels

  day 5

Study Arms (2)

Linagliptin

EXPERIMENTAL

Linagliptin 5 mg tablets daily for 4 days

Drug: Linagliptin

Placebo

PLACEBO COMPARATOR

Placebo tablets 1 daily for 4 days

Drug: Placebo

Interventions

Linagliptin DRUG

Linagliptin 5 mg tablets for 4 days

Also known as: Trajenta 5 mg

Linagliptin

Placebo DRUG

Placebo tablets for 4 days

Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• eGFR \> 60 mL/min/1.73 mq (for the patients without renal failure)
• eGFR 10-60 mL/min/1.73 mq (for the patients with renal failure)

You may not qualify if:

• Type 1 diabetes
• Hypersensitivity to Linagliptin or excipients
• Intolerance to other DPP-4 inhibitors
• Terminal renal failure (eGFR \< 10 mL/min/1.73 mq)
• Use of GLP-1 analogs or other DPP-4 inhibitors
• Recent (within 1 month) trauma or surgery or acute diseases
• Any acute or chronic inflammatory condition
• Immunosuppression or organ transplantation
• Pregnancy or lactation
• Inability to provide informed consent.

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

University Hospital Diabetes Outpatient Clinic

Padua, 35100, Italy

Location

Related Publications (2)

• Fadini GP, Bonora BM, Albiero M, Zaninotto M, Plebani M, Avogaro A. DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes. Cardiovasc Diabetol. 2017 Feb 10;16(1):22. doi: 10.1186/s12933-017-0507-9.

  PMID: 28183314 DERIVED

• Fadini GP, Bonora BM, Cappellari R, Menegazzo L, Vedovato M, Iori E, Marescotti MC, Albiero M, Avogaro A. Acute Effects of Linagliptin on Progenitor Cells, Monocyte Phenotypes, and Soluble Mediators in Type 2 Diabetes. J Clin Endocrinol Metab. 2016 Feb;101(2):748-56. doi: 10.1210/jc.2015-3716. Epub 2015 Dec 22.

  PMID: 26695864 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Kidney Failure, Chronic; Diabetes Mellitus; Inflammation

Interventions

Linagliptin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Officials

• Angelo Avogaro, M.D. Ph.D.

  University of Padova

  STUDY CHAIR

• Gian Paolo Fadini, M.D.

  University of Padova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2012
• First Posted: June 12, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 19, 2014

Record last verified: 2014-12

Locations

IT (1)