Sitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Information source: University Health Network, Toronto
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hyperlipidemia
Intervention: Sitagliptin (Drug)
Phase: N/A
Status: Completed
Sponsored by: University Health Network, Toronto Official(s) and/or principal investigator(s): Gary Lewis, MD, Principal Investigator, Affiliation: UHN
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.
Clinical Details
Official title: Sitagliptin (®Januvia) Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science
Primary outcome: The Primary Objective is to Examine the apoB48 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo), Under Conditions of a Pancreatic Clamp and a Steady State Fed State
Secondary outcome: The Primary Objective is to Examine the apoB100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo), Under Conditions of a Pancreatic Clamp and a Steady State Fed State
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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.
Locations and Contacts
Toronto General Hospital, Toronto, Ontario M5G 2C4, Canada
Additional Information
Starting date: July 2012
Last updated: April 2, 2014
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