GLP-1 Mediating DPP-4 Inhibition in Type 2 Diabetes

NCT02639130 | Completed Phase 4

• 1 other identifier: DZBL-2007-1
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the extent to which the effects of treatment with LAF237 100 mg QD on glucagon secretion are mediated by Glucagon-like-peptide 1 (GLP-1) in type 2 diabetic patients and healthy subjects.

Conditions

Type 2 Diabetes

Keywords

Gastric Inhibitory Polypeptide (GIP); Glucagon-Like Peptide 1 (GLP-1); DPP-4 inhibition; Exendin [9-39]; Gastric emptying; Glucagon; Incretin; Insulin Secretion; Normal glucose-tolerant

Outcome Measures

Primary Outcomes (2)

• Ratio of integrated insulin secretion rates (total AUC ISR) over 4 hour following the meal

  4 hour following the meal

• total AUC Glucose over 4 hour following the meal

  4 hour following the meal

Study Arms (2)

Vildagliptin

ACTIVE COMPARATOR

After a screening examination, patients were treated with vildagliptin and participated in meal tests (day 9 and 10, respectively), in a crossover design. Between the two treatment periods, there was a ≥ 5 week wash-out period. Experimental procedures: Meal test, determination of the rate of gastric emptying. On days 9 and 10 of treatment, the volunteers underwent a mixed meal (one scrambled egg, a slice of ham, 10 g of butter, two slices of toast, 20 g strawberry jam, and 200 ml of unsweetened tea) test in the morning after fasting overnight. 13C-octanoic acid (110 µl/100 mg) was used as label. Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin \[9-39\].

Drug: Exendin [9-39]; Drug: Placebo

Placebo

PLACEBO COMPARATOR

After a screening examination, patients were treated with placebo, and participated in meal tests (day 9 and 10, respectively), in a crossover design. Between the two treatment periods, there was a ≥ 5 week wash-out period. Experimental procedures: Meal test, determination of the rate of gastric emptying. On days 9 and 10 of treatment, the volunteers underwent a mixed meal (one scrambled egg, a slice of ham, 10 g of butter, two slices of toast, 20 g strawberry jam, and 200 ml of unsweetened tea) test in the morning after fasting overnight. 13C-octanoic acid (110 µl/100 mg) was used as label. Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin \[9-39\].

Drug: Exendin [9-39]; Drug: Placebo

Interventions

Exendin [9-39] DRUG

Exendin \[9-39\] at 350 and 500 pmol/kg/min for infusion as challenge agent

Also known as: (GLP-1 receptor antagonist)

Placebo; Vildagliptin

Placebo DRUG

Placebo infusion as challenge agent

Placebo; Vildagliptin

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment with either diet/exercise or metformin
• HbA1c 6.5 - 9.0 %
• Fasting plasma glucose 6.0 - 11.0 mmol/l
• Body-mass-index 20.0 - 35.0 kg/m²
• Healthy controls were required to have a normal oral glucose tolerance test (75g) and no first-degree relatives with type 2 diabetes nor a personal history of gestational diabetes

You may not qualify if:

• Significant heart, kidney (serum creatinine ≤ 123 µmol/l in woman and ≤ 132 µmol/l in men), liver (transaminases \< 2fold upper limit of normal) and gastrointestinal disease

Sponsors & Collaborators

• Diabeteszentrum Bad Lauterberg im Harz: lead

Study Sites (1)

Diabeteszentrum Bad Lauterberg

Bad Lauterberg im Harz, Lower Saxony, 37431, Germany

Location

Related Publications (1)

• Nauck MA, Kind J, Kothe LD, Holst JJ, Deacon CF, Broschag M, He YL, Kjems L, Foley J. Quantification of the Contribution of GLP-1 to Mediating Insulinotropic Effects of DPP-4 Inhibition With Vildagliptin in Healthy Subjects and Patients With Type 2 Diabetes Using Exendin [9-39] as a GLP-1 Receptor Antagonist. Diabetes. 2016 Aug;65(8):2440-7. doi: 10.2337/db16-0107. Epub 2016 Apr 5.

  PMID: 27207543 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

exendin (9-39)

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michael A. Nauck, Prof.

  Diabeteszentrum Bad Lauterberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Michael A. Nauck

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 24, 2015
• Study Start: February 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: August 16, 2016

Record last verified: 2016-08

Locations

DE (1)