Back to resultsSitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Primary Purpose
Hyperlipidemia
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Sitagliptin
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Hyperlipidemia focused on measuring Intestinal lipoprotein, Apolipoprotein B48 and apolipoprotein B100, Pancreatic clamp, DPPIV inhibitor
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Toronto General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sitagliptin
Placebo
Arm Description
sitagliptin, 100mg, oral, single dose
Placebo, oral, single dose
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Apolipoprotein B100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
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.
Full Information
NCT ID
NCT01600703
First Posted
May 15, 2012
Last Updated
January 20, 2017
Sponsor
University Health Network, Toronto
Collaborators
Merck Frosst Canada Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01600703
Brief Title
Sitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Official Title
Sitagliptin (®Januvia) Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
Merck Frosst Canada Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipidemia
Keywords
Intestinal lipoprotein, Apolipoprotein B48 and apolipoprotein B100, Pancreatic clamp, DPPIV inhibitor
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitagliptin
Arm Type
Experimental
Arm Description
sitagliptin, 100mg, oral, single dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, oral, single dose
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia
Intervention Description
Sitagliptin, 100mg, oral, single dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, oral, single dose
Primary Outcome Measure Information:
Title
Apolipoprotein B48 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
Description
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.
Time Frame
10 hours
Secondary Outcome Measure Information:
Title
Apolipoprotein B100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
Description
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.
Time Frame
10 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Lewis, MD
Organizational Affiliation
UHN
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
24584549
Citation
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.
Results Reference
result
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Sitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
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