Linagliptin's Effect on CD34+ Stem Cells

NCT02467478 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 121439
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes is a national epidemic. Diabetes has undesirable effects on blood vessels which may contribute to heart disease. Endothelial Progenitor Cells (EPCs) are found in the blood. Research has shown that improving the survival of these special blood cells may decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart disease. Linagliptin is an Food and Drug Administration (FDA) approved prescription medicine used along with insulin or with oral medications to lower blood sugar in people with Type 2 diabetes. It is in a class of diabetes medication called Dipeptidyl peptidase-4 (DPP-4) inhibitors. DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2 diabetes. Hypothesis: Both type 2 diabetes and Chronic Kidney Disease (CKD) are associated with poor stem cell number and function. Poor viability and function of EPCs in CKD and diabetes The investigators hypothesize that use of Linagliptin (along with Insulin) may help reduce cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control

Conditions

Type 2 Diabetes; Impaired Renal Function

Keywords

Diabetes Mellitus, Type 2; Endothelial cells; Cellular biomarker; endothelial dysfunction; CD34+; Impaired renal function

Outcome Measures

Primary Outcomes (2)

• Cellular Markers

  The investigators will use participants' peripheral blood derived CD34+ cells looking at number, function, and gene expression. Post Linagliptin will be compared to pre Linagliptin measurements. Here we report fold changes in protein populations as determined by ELISA.

  Week 12 expression as a fold difference to Week 0

• Urinary Function Marker in CKD

  We measure using microalbumin/creatinine ratio provided from a random spot urine sample.

  12 weeks post beginning Linagliptin or placebo treatment

Secondary Outcomes (11)

• Serum Endothelial Inflammatory Markers

  12 weeks post Linagliptin or Placebo treatment

• Serum Endothelial Inflammatory Markers

  12 weeks post Linagliptin or Placebo treatment

• Fasting Lipid Profile

  12 weeks post beginning Linagliptin or placebo treatment

• Glycemic Control

  12 weeks post beginning Linagliptin or placebo treatment

• Glycemic Control: Fasting Glucose

  12 weeks post beginning Linagliptin or placebo treatment

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo 1 pill daily for 12 weeks

Drug: Placebo

Linagliptin

ACTIVE COMPARATOR

Linagliptin 5mg once daily for 12 weeks

Drug: Linagliptin

Interventions

Linagliptin DRUG

5 mg tablet once daily for 12 weeks

Also known as: TRADJENTA

Linagliptin

Placebo DRUG

1 tablet daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 30-70 years
• Diagnosis of type 2 diabetes within the previous 15 years using criteria of the American Diabetes Association
• Currently being treated with 1-2 grams/day of metformin, or insulin or both stably
• Hemoglobin A1c (HbA1C) between 6.5% to 10.0% (both inclusive)
• Body Mass Index (BMI) between 25 and 39.9 kg/m2 (both inclusive)
• Chronic Kidney disease (CKD) Stages 1-3, Creatinine clearance (CrCl) less than 90 and more than 29

You may not qualify if:

• Type 1 diabetes
• History of Diabetic Ketoacidosis (DKA) or hyperosmolar nonketotic coma
• Hemoglobinopathies with low hematocrit (Below 28 Units)
• History of pancreatitis
• History of cancer within the past 5 years (except basal cell carcinoma)
• Previous cardiovascular or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or Peripheral Vascular Disease (PVD)
• Statin use started in the last 3 month
• Current use of oral or injectable anti-diabetic medication other than Metformin and insulin
• Consistent use of steroids within the last 3 months
• Any active wounds, or surgery within the past 3 months
• Inflammatory disease, or the chronic use of anti-inflammatory drugs within the past 3 months
• Untreated hyper/hypothyroidism
• Contraindications to moderate exercise
• Implanted devices that might interact with the tanita scale
• Pre-existing liver disease and/or Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) \> 2.5 times Under the Normal Limits (UNL)

Sponsors & Collaborators

• George Washington University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

The George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Related Publications (1)

• Awal HB, Nandula SR, Domingues CC, Dore FJ, Kundu N, Brichacek B, Fakhri M, Elzarki A, Ahmadi N, Safai S, Fosso M, Amdur RL, Sen S. Linagliptin, when compared to placebo, improves CD34+ve endothelial progenitor cells in type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin: a randomized controlled trial. Cardiovasc Diabetol. 2020 Jun 3;19(1):72. doi: 10.1186/s12933-020-01046-z.

  PMID: 32493344 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency

Interventions

Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Limitations may include the relatively short duration of 12-week Linagliptin therapy. Limitations also arise because of the small sample size, and due to the difficulty in obtaining all cellular outcome measures, in some patients, due to low total CD34+ cell numbers. Further studies with a larger population and longer duration may be helpful to further define the mechanisms behind our findings.

Results Point of Contact

• Title: Sabyasachi Sen
• Organization: GW MFA

ssen1@gwu.edu

3014616676

Study Officials

• Sabyasachi Sen, MD, PhD

  Medical Faculty Associates

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: June 10, 2015
• Study Start: April 1, 2015
• Primary Completion: April 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 19, 2023
• Results First Posted: January 19, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)