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

Hyperlipidemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01600703
• Other study ID #: Sitagliptin-REB-09-0428-B
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 15, 2012
• Last updated: January 20, 2017
• Start date: July 2012
• Est. completion date: August 2013

Study information

• Verified date: January 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Drug:
• Sitagliptin
Sitagliptin, 100mg, oral, single dose
• Placebo
Placebo, oral, single dose

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Merck Frosst Canada Ltd.

Country where clinical trial is conducted

Canada, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	10 hours