Clinical trial NCT02180334: The Effect of Combination of Mosapride and DPP-4 Inhibitor on Plasma Concentration of Incretin Hormones
Official title: The Effect of Combination of Mosapride and Dipeptidyl Peptidase-4 (DPP-4) Inhibitor on Plasma Concentration of Incretin Hormones
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Gastric Emptying
Gastrointestinal Motility
Incretins
Glucagon-Like Peptide 1
Diabetes Mellitus
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Daewoong Pharmaceutical Co. LTD.
First posted: 2014-07-02
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to investigate the effects of combined administration of mosapride as modulator of gastrointestinal motility and DPP-4 inhibitor on secretion of gut hormone such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), and oral glucose tolerance. Additionally, change in lipid profile and insulin secretion will be also assessed.

Detailed description: This is randomized, double-blind, placebo-controlled, cross-over study. After screening and enrollment, participants will take 5 mg of linagliptin once a day for one week of run-in period (Day 1 to Day 7). Randomization will be done on Day 8 to assign the participants to either mosapride arm or placebo arm. If a subject is assigned to mosapride arm, mixed meal tolerance test (MMTT) will be performed after taking mosapride with linagliptin. If a subject is assigned to placebo arm, he/she will take placebo instead of mosapride before MMTT. On Day 9, all subjects will be crossed over to the other arm and MMTT will proceed with medication depending on their arms. Gastric emptying time measurement with paracetamol will be done along with MMTT. Plasma incretin hormone levels in two arms will be compared.

Eligibility criteria: Inclusion Criteria:

* type 2 diabetes mellitus
* BMI \< 35 kg/m2
* HbA1c 6.5\~8.0% for whom is on lifestyle modification only, 6.0\~8.0% for whom is taking oral antidiabetic drug(s).
* on lifestyle modification or oral antidiabetic therapy (sulfonylurea, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and DPP-4 inhibitors)
* Who read and signed the informed consent agreement

Exclusion Criteria:

* chronic disease(s) requiring medication other than diabetes mellitus
* type 1 diabetes mellitus or history of diabetic ketoacidosis
* on insulin therapy or requiring insulin therapy
* history of gastrointestinal surgery excluding appendectomy, hernia repair and hemorrhoid surgery
* serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) to be more than 2.5 times above the upper limit of normal
* estimated glomerular filtration rate to be less than 50 mL/min/1.73m2
* genetic disorders associated with digestion and absorption such as galactose intolerance, Lapp lactase deficiency, and glucose-galactose malabsorption
* history of hypersensitivity including anaphylaxis and angioedema to mosapride citrate, linagliptin, or paracetamol (acetaminophen)
* history of asthma associated with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
* currently taking drugs that can prolong QT interval, including procainamide, quinidine, flecainide, sotalol, tricyclic antidepressants
* currently taking anticholinergics such as atropine sulfate, scopolamine butylbromide
* child-bearing or lactating women
* women in reproductive age who disagree with contraception with proper method or urine pregnancy test during the study period

Primary outcomes:
measure: Area under the curve (AUC) of plasma total GLP-1 levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Secondary outcomes:
measure: Area under the curve (AUC) of plasma total GIP levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of plasma glucose levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of plasma insulin levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of plasma C-peptide levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of serum triglyceride levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of serum nonesterified fatty acid (NEFA) levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: Area under the curve (AUC) of plasma active GLP-1 levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Other outcomes:
measure: Area under the curve (AUC) of plasma paracetamol levels
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: The peak concentration of plasma paracetamol
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
measure: The time to peak concentration of plasma paracetamol
timeFrame: 0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University College of Medicine
name: Young Min Cho, MD, PHD
role: STUDY_CHAIR
References: