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

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ClinicalTrials.gov Identifier: NCT01600703
Recruitment Status : Completed
First Posted : May 17, 2012
Results First Posted : May 5, 2014
Last Update Posted : January 23, 2017
Sponsor:
Collaborator:
Merck Frosst Canada Ltd.
Information provided by (Responsible Party):
University Health Network, Toronto

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hyperlipidemia Drug: Sitagliptin Drug: Placebo Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Sitagliptin (®Januvia) Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Study Start Date : July 2012
Actual Primary Completion Date : May 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Sitagliptin
sitagliptin, 100mg, oral, single dose
 Drug: Sitagliptin
Sitagliptin, 100mg, oral, single dose
Other Name: Januvia
Placebo Comparator: Placebo
Placebo, oral, single dose
 Drug: Placebo
Placebo, oral, single dose


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01600703


Locations
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Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Merck Frosst Canada Ltd.
Investigators
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Principal Investigator: Gary Lewis, MD UHN
More Information
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Publications of Results:

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01600703    
Other Study ID Numbers: Sitagliptin-REB-09-0428-B
First Posted: May 17, 2012    Key Record Dates
Results First Posted: May 5, 2014
Last Update Posted: January 23, 2017
Last Verified: January 2013
Keywords provided by University Health Network, Toronto:
Intestinal lipoprotein
Apolipoprotein B48 and apolipoprotein B100
Pancreatic clamp
DPPIV inhibitor
Additional relevant MeSH terms:
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Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
 Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action