Sitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans

NCT01600703 | Completed Phase 2 Results

• 1 other identifier: Sitagliptin-REB-09-0428-B
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Recent studies in both animals and humans has demonstrated that the hormone GLP-1 (glucagon like peptide 1) reduces intestinal production of lipoprotein particles. The investigators therefore hypothesise that the drug sitagliptin which prevents the breakdown of GLP-1 will reduce intestinal lipoprotein production in humans. The investigators are unable to speculate whether sitagliptin will affect hepatic lipoprotein production because of lack of of data from animal studies or in vitro data. Sitagliptin is already an approved treatment for type 2 diabetes.

Conditions

Hyperlipidemia

Keywords

Intestinal lipoprotein; Apolipoprotein B48 and apolipoprotein B100; Pancreatic clamp; DPPIV inhibitor

Outcome Measures

Primary Outcomes (1)

• Apolipoprotein B48 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)

  Apolipoprotein B48 turnover was measured in a 10-hour kinetic study with in vivo tracer techniques and mathematical modeling to calculate production rates. Studies were performed under conditions of a pancreatic clamp and a steady state fed state in volunteers receiving single oral dose of either 100mg sitagliptin or matching placebo.

  10 hours

Secondary Outcomes (1)

• Apolipoprotein B100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)

  10 hours

Study Arms (2)

Sitagliptin

EXPERIMENTAL

sitagliptin, 100mg, oral, single dose

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Placebo, oral, single dose

Drug: Placebo

Interventions

Sitagliptin DRUG

Sitagliptin, 100mg, oral, single dose

Also known as: Januvia

Sitagliptin

Placebo DRUG

Placebo, oral, single dose

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged 18 to 60 years
• Body mass index 20 kg/m2 to 27 kg/m2
• Hemoglobin above 130g/L.
• Normal glucose tolerance in response to a 75g, 2-hr OGTT

You may not qualify if:

• Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr \> 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP \> 100 or systolic \> 180) or proliferative retinopathy
• History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.
• Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
• Any laboratory values: AST \> 2x ULN; ALT \> 2x ULN TSH \> 6 mU/l
• Current addiction to alcohol or substances of abuse as determined by the investigator.
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
• Taking any prescription or non-prescription medications at the time of the study
• Having donated blood three months prior to and three months post study procedures
• A pregnancy test will be performed 1 to 3 days prior to each study in all female subjects. Those who test positive for pregnancy will be excluded.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Merck Frosst Canada Ltd.: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• Xiao C, Dash S, Morgantini C, Patterson BW, Lewis GF. Sitagliptin, a DPP-4 inhibitor, acutely inhibits intestinal lipoprotein particle secretion in healthy humans. Diabetes. 2014 Jul;63(7):2394-401. doi: 10.2337/db13-1654. Epub 2014 Feb 28.

  PMID: 24584549 RESULT

MeSH Terms

Conditions

Hyperlipidemias

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Dr. Gary Lewis
• Organization: University Health Network

gary.lewis@uhn.ca

416-340-4270

Study Officials

• Gary Lewis, MD

  UHN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2012
• First Posted: May 17, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: August 1, 2013
• Last Updated: January 23, 2017
• Results First Posted: May 5, 2014

Record last verified: 2013-01

Locations

CA (1)