Pre-diabetesPhase 4NCT00364377
Incretins in Impaired Fasting Glucose
A Phase 4 study testing Sitagliptin in people with Pre-diabetes, run by Mayo Clinic at 1 site in United States.
Trial summary
People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Pre-diabetes
- What is being tested?
- Sitagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Dec 2008
- Phase
- Phase 4
- 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 35 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females between the ages of 35-70.
- Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening.
- Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.
Who cannot join
- Individuals with a body mass index less than 19 or greater than 40 kg/m^2, or a total weight > 130 kg, will be excluded from study.
- Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes.
- No history of a) significant nephropathy, (i.e., plasma creatinine > 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness.
- Pregnant or lactating females.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.
Read the detailed description
Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion.
Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.
The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.
- Conditions
- Pre-diabetes
- Being tested
- Sitagliptin, Placebo
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
Also called Januvia
100 mg once daily
PlaceboOther
once daily for duration of the study
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin | Active comparator | People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily. Receives: Drug: Sitagliptin |
| Placebo | Placebo comparator | People with impaired fasting glucose randomized to treatment with placebo once daily. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lowering of Fasting Glucose
fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2006 (estimated)
- Study startAug 2006
- Primary completionDec 2008
- Study completionDec 2008
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 Pre-diabetesStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adrian Vella, Mayo Clinic
- Investigators
- Adrian Vella, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00364377
- Sponsor's protocol ID
- 06-002673
- Status last verified
- Nov 2011
- First submitted
- 14 Aug 2006
- Last updated
- 6 Dec 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bock G, Dalla Man C, Micheletto F, Basu R, Giesler PD, Laugen J, Deacon CF, Holst JJ, Toffolo G, Cobelli C, Rizza RA, Vella A. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf). 2010 Aug;73(2):189-96. doi: 10.1111/j.1365-2265.2009.03764.x. Epub 2009 Dec 18.
PubMed 20039889
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
- ClinicalTrials.gov ID
- NCT00364377
- Acronym / sponsor ID
- 06-002673
- Conditions
- Pre-diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 15 Aug 2006 (estimated)
- Results
- Posted 6 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.
Detailed description
Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion.
Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.
The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin | Active comparator | Drug: SitagliptinPeople with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily. |
| Placebo | Placebo comparator | Other: PlaceboPeople with impaired fasting glucose randomized to treatment with placebo once daily. |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males and females between the ages of 35-70.
- Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening.
- Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.
Key exclusion criteria (4 listed)
- Individuals with a body mass index less than 19 or greater than 40 kg/m^2, or a total weight > 130 kg, will be excluded from study.
- Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes.
- No history of a) significant nephropathy, (i.e., plasma creatinine > 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness.
- Pregnant or lactating females.
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: Januvia100 mg once daily | Drug | Sitagliptin |
| Placeboonce daily for duration of the study | Other | Placebo |
Primary outcome
Lowering of Fasting Glucose
Time frame: 8 weeks
fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20039889Bock G, Dalla Man C, Micheletto F, Basu R, Giesler PD, Laugen J, Deacon CF, Holst JJ, Toffolo G, Cobelli C, Rizza RA, Vella A. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf). 2010 Aug;73(2):189-96. doi: 10.1111/j.1365-2265.2009.03764.x. Epub 2009 Dec 18.
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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.
Adrian Vella, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sitagliptin in people with Pre-diabetes, run by Mayo Clinic at 1 site in United States.
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 3 inclusion and 4 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 6 Dec 2011. 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 United States. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 6 Dec 2011). 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?
Lowering of Fasting Glucose (time frame: 8 weeks). 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 NCT00364377, 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 6 Dec 2011.