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

January 20, 2017 updated by: University Health Network, Toronto

Sitagliptin (®Januvia) Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Each subject will be studied twice 4-6 weeks apart in random order in this single blinded study. In study A they will receive a single dose of sitagliptin 100mg od. In study B they will receive placebo. A nasoduodenal tube will be sited under fluoroscopic guidance the day prior to the study. On the day of the study regular liquid formula (Great shake plus) will be infused from 4am through the tube to maintain a constant fed state. A pancreatic clamp (octreotide with replacement glucose, insulin and growth hormone) along with saline/sitagliptin will be started at 7am. From 9am an iv bolus of deuterated-glycerol (d5-glycerol) along with a regular infusion of deuterated leucine (L-[5,5,5-2H3]. Regular blood samples will be drawn to assess lipoprotein kinetics.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
  2. 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
  3. History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.
  4. 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.
  5. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l
  6. Current addiction to alcohol or substances of abuse as determined by the investigator.
  7. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
  8. Taking any prescription or non-prescription medications at the time of the study
  9. Having donated blood three months prior to and three months post study procedures
  10. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sitagliptin
sitagliptin, 100mg, oral, single dose
Drug: Sitagliptin
Sitagliptin, 100mg, oral, single dose
Other Names:
  • Januvia
Placebo Comparator: Placebo
Placebo, oral, single dose
Drug: Placebo
Placebo, oral, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apolipoprotein B48 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
Time Frame: 10 hours
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apolipoprotein B100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
Time Frame: 10 hours
Apolipoprotein B100 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Merck Frosst Canada Ltd.

Investigators

  • Principal Investigator: Gary Lewis, MD, UHN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

May 15, 2012

First Submitted That Met QC Criteria

May 16, 2012

First Posted (Estimate)

May 17, 2012

Study Record Updates

Last Update Posted (Estimate)

January 23, 2017

Last Update Submitted That Met QC Criteria

January 20, 2017

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sitagliptin-REB-09-0428-B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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