HyperlipidemiaPhase 2/3NCT01600703
Sitagliptin Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
A Phase 2/3 study testing Sitagliptin in people with Hyperlipidemia, run by University Health Network, Toronto at 1 site in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperlipidemia
- What is being tested?
- Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2012to Aug 2013
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hyperlipidemia
- Being tested
- Sitagliptin, Placebo
- Keywords
- Intestinal lipoprotein, Apolipoprotein B48 and apolipoprotein B100, Pancreatic clamp, DPPIV inhibitor
- Medical subject headings
- Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
Also called Januvia
Sitagliptin, 100mg, oral, single dose
PlaceboDrug
Placebo, oral, single dose
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin | Experimental | sitagliptin, 100mg, oral, single dose Receives: Drug: Sitagliptin |
| Placebo | Placebo comparator | Placebo, oral, single dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 hours
Secondary outcomes (1)
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.
Measured: 10 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2012 (estimated)
- Study startJul 2012
- Primary completionMay 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Frosst Canada Ltd.
- Responsible party
- Sponsor
- Investigators
- Gary Lewis, MD, Principal investigator, UHN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01600703
- Sponsor's protocol ID
- Sitagliptin-REB-09-0428-B
- Status last verified
- Jan 2013
- First submitted
- 15 May 2012
- Last updated
- 23 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24584549
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sitagliptin (®Januvia) Regulation of Intestinal and Hepatic Lipoprotein Particle and Hepatic Glucose Production in Humans
- ClinicalTrials.gov ID
- NCT01600703
- Acronym / sponsor ID
- Sitagliptin-REB-09-0428-B
- Conditions
- Hyperlipidemia
- Keywords
- Intestinal lipoprotein, Apolipoprotein B48 and apolipoprotein B100, Pancreatic clamp, DPPIV inhibitor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Merck Frosst Canada Ltd.
- Study start
- Jul 2012
- Primary completion
- May 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 17 May 2012 (estimated)
- Results
- Posted 5 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin | Experimental | Drug: Sitagliptinsitagliptin, 100mg, oral, single dose |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, oral, single dose |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinAlso: JanuviaSitagliptin, 100mg, oral, single dose | Drug | Sitagliptin |
| PlaceboPlacebo, oral, single dose | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Apolipoprotein B100 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo)
Time frame: 10 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24584549Xiao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Lewis, MD principal investigator
UHN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sitagliptin in people with Hyperlipidemia, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apolipoprotein B48 Production Rate After Acute Oral Administration of 100mg Sitagliptin (Compared to Placebo) (time frame: 10 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01600703, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2017.