Pre-diabetesNCT01488279
Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy
A study testing Dexamethasone 2.5 mg and Sitagliptin 100 mg in people with Pre-diabetes and Impaired Fasting Glucose, run by University of Vermont at 1 site in United States.
Trial summary
The investigators hypothesize that sitagliptin will significantly reduce impairments in insulin secretion and insulin resistance resulting from short-term oral glucocorticoid therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pre-diabetes, Impaired Fasting Glucose, Impaired Glucose Tolerance
- What is being tested?
- Dexamethasone 2.5 mg and Sitagliptin 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Dec 2015
- Phase
- Interventional
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women
- impaired fasting glucose
- We will stratify for weight and age.
Who cannot join
- Known Type 2 DM
- Severe disease preventing participation in study
- On chronic steroids for any reason
- Already taking DPP-4 inhibitor
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Vermont Clinical Research Center
South Burlington, Vermont, 05403
About this study
The investigators hypothesize that sitagliptin will significantly reduce impairments in insulin secretion and insulin resistance resulting from short-term oral glucocorticoid therapy.
Read the detailed description
The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled parallel arm crossover study comparing insulin secretion and insulin resistance in subjects with impaired fasting glucose on oral glucocorticoid therapy + placebo versus subjects on oral glucocorticoid therapy + sitagliptin. For the oral glucocorticoid therapy, we plan to use dexamethasone (dex) 2.5 mg daily. We chose dex for known glycemic effects, improved compliance, and once daily dosing.
Previous studies have shown that in humans, glucocorticoid-induced insulin resistance develops within 4 hours with infused drug at high dose (methylprednisolone 500 mg x single infusion) and does not change with duration of drug therapy of up to 3 months.10 Furthermore, more modest doses over a short duration (dex 2.0 mg orally daily x 2 days) have been shown to decrease insulin-mediated glucose disposal.11 12 Thus, studying acute effects of oral dex at 2.5 mg daily x 7 days should be more than adequate to achieve impaired glucose-mediated insulin secretion and impaired insulin-mediated glucose disposal.
In order for sitagliptin to have the desired effect, drug should be administered for at least 7 days (5 half-lives plus 40% more for margin of error). We plan to study subjects with impaired fasting glucose or impaired glucose tolerance as they would likely be candidates for DPP-IV therapy in the future and would be likely to have impaired insulin secretion and impaired glucose disposal amenable to DPP-IV therapy.
A total of 10 participants were enrolled in this study. Participants were given 2.5 mg dexamethasone daily plus either placebo tablet or sitagliptin daily for 8 days with a washout period prior to crossover. The order of study drug administration was randomized. Participants underwent blood sampling, mixed meal testing (MMT), and intravenous glucose tolerance testing (IVGTT) before and after each study period.
- Being tested
- Dexamethasone 2.5 mg and Sitagliptin 100 mg, Dexamethasone 2.5 mg and placebo tablet
- Keywords
- Pre-diabetes, Impaired fasting glucose, Impaired glucose tolerance, Steroid-induced hyperglycemia
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone 2.5 mg and Sitagliptin 100 mgDrug
Also called Sitagliptin
Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days
Dexamethasone 2.5 mg and placebo tabletDrug
Also called Placebo
Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone 2.5mg and Sitagliptin100mg | Active comparator | Participants received Dexamethasone 2.5 mg plus Sitagliptin 100 mg daily for 8 days Receives: Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg; Drug: Dexamethasone 2.5 mg and placebo tablet |
| Dexamethasone 2.5mg and placebo tablet | Placebo comparator | Participants received Dexamethasone 2.5 mg plus Sitagliptin-matched placebo tablet daily for 8 days. Receives: Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg; Drug: Dexamethasone 2.5 mg and placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Insulin Sensitivity measured at the end of each treatment period. The primary outcome variable was the difference in the disposition index (DI) determined as the product of the acute insulin response to glucose (AIRg) x the insulin sensitivity index (SI) in subjects during IVGTT on the 8th day (after 7 days) of on dex + placebo, then a after a washout of approximately 4 weeks, participants crossed over to dex + sitagliptin 100 mg x 7 days. Subjects were randomized to order of medication. The primary analyses will be an ANCOVA, including baseline responses as a covariate.
Measured: Measured on day #8 (after 8 days of sitagliptin or placebo) followed by a 4 week washout then measured again on day #8 (after 8 days of crossover treatment).
Secondary outcomes (4)
Change in Active GIP
We had planned to measure the difference or change in active GIP in response to the MTT between the 2 study drug periods: on sitagliptin versus on placebo. However, when other measures were negative, we opted not to pursue this lab assay for cost and time. We did not perform measures of GIP.
Measured: Active GIP would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GIP
Change in Active GLP-1
As with GIP, we had planned to measure the difference or change in active GLP-1 in response to the MTT between the 2 study drug periods: on sitagliptin versus on placebo. We had hypothesized that GIP and GLP-1 would be elevated while on the DPP4 inhibitor compared to placebo as this is the mechanism of action of the drug sitagliptin. When other measures were negative, we elected not to pursue this due to time and cost.
Measured: Active GLP-1 would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GLP-1
Change in Glucose Response
Change in glucose response during the MTT. This was the Si (insulin sensitivity). We sought to determine whether there was an improvement in the glucose response after a meal on the DPP4i compared to placebo in the face of steroid (dexamethasone).
Measured: measured on day #9 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #9 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT
Change in Insulin Secretion (AIRg or Acute Insulinogenic Response to Glucose)
We measured the change in insulin secretion (AIRg or acute insulinogenic response to glucose) during the MTT and compared the insulin secretion on the DPP4 inhibitor (sitagliptin) compared to placebo. We had expected the AIRg to be greater with DPP4i compared to placebo.
Measured: measured twice: on day #8 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #8 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2011 (estimated)
- Study startSep 2012
- Primary completionJul 2014
- Study completionDec 2015
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.
- Other trials for Pre-diabetesStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind, placebo controlled crossover study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Annis Marney, MD, MSCI, University of Vermont
- Investigators
- Annis M Marney, MD, MSCI, Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488279
- Sponsor's protocol ID
- MISP 39681
- Status last verified
- Feb 2018
- First submitted
- 5 Dec 2011
- Last updated
- 12 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy
- ClinicalTrials.gov ID
- NCT01488279
- Acronym / sponsor ID
- MISP 39681
- Keywords
- Pre-diabetes, Impaired fasting glucose, Impaired glucose tolerance, Steroid-induced hyperglycemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 8 Dec 2011 (estimated)
- Results
- Posted 9 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that sitagliptin will significantly reduce impairments in insulin secretion and insulin resistance resulting from short-term oral glucocorticoid therapy.
Detailed description
The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled parallel arm crossover study comparing insulin secretion and insulin resistance in subjects with impaired fasting glucose on oral glucocorticoid therapy + placebo versus subjects on oral glucocorticoid therapy + sitagliptin. For the oral glucocorticoid therapy, we plan to use dexamethasone (dex) 2.5 mg daily. We chose dex for known glycemic effects, improved compliance, and once daily dosing.
Previous studies have shown that in humans, glucocorticoid-induced insulin resistance develops within 4 hours with infused drug at high dose (methylprednisolone 500 mg x single infusion) and does not change with duration of drug therapy of up to 3 months.10 Furthermore, more modest doses over a short duration (dex 2.0 mg orally daily x 2 days) have been shown to decrease insulin-mediated glucose disposal.11 12 Thus, studying acute effects of oral dex at 2.5 mg daily x 7 days should be more than adequate to achieve impaired glucose-mediated insulin secretion and impaired insulin-mediated glucose disposal.
In order for sitagliptin to have the desired effect, drug should be administered for at least 7 days (5 half-lives plus 40% more for margin of error). We plan to study subjects with impaired fasting glucose or impaired glucose tolerance as they would likely be candidates for DPP-IV therapy in the future and would be likely to have impaired insulin secretion and impaired glucose disposal amenable to DPP-IV therapy.
A total of 10 participants were enrolled in this study. Participants were given 2.5 mg dexamethasone daily plus either placebo tablet or sitagliptin daily for 8 days with a washout period prior to crossover. The order of study drug administration was randomized. Participants underwent blood sampling, mixed meal testing (MMT), and intravenous glucose tolerance testing (IVGTT) before and after each study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double blind, placebo controlled crossover study
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone 2.5mg and Sitagliptin100mg | Active comparator | Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg, Drug: Dexamethasone 2.5 mg and placebo tabletParticipants received Dexamethasone 2.5 mg plus Sitagliptin 100 mg daily for 8 days |
| Dexamethasone 2.5mg and placebo tablet | Placebo comparator | Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg, Drug: Dexamethasone 2.5 mg and placebo tabletParticipants received Dexamethasone 2.5 mg plus Sitagliptin-matched placebo tablet daily for 8 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Men and women
- impaired fasting glucose
- We will stratify for weight and age.
Key exclusion criteria (4 listed)
- Known Type 2 DM
- Severe disease preventing participation in study
- On chronic steroids for any reason
- Already taking DPP-4 inhibitor
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 |
|---|---|---|
| Dexamethasone 2.5 mg and Sitagliptin 100 mgAlso: SitagliptinParticipants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days | Drug | Dexamethasone 2.5mg and Sitagliptin100mg, Dexamethasone 2.5mg and placebo tablet |
| Dexamethasone 2.5 mg and placebo tabletAlso: PlaceboParticipants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days | Drug | Dexamethasone 2.5mg and Sitagliptin100mg, Dexamethasone 2.5mg and placebo tablet |
Primary outcome
Insulin Sensitivity
Time frame: Measured on day #8 (after 8 days of sitagliptin or placebo) followed by a 4 week washout then measured again on day #8 (after 8 days of crossover treatment).
Insulin Sensitivity measured at the end of each treatment period. The primary outcome variable was the difference in the disposition index (DI) determined as the product of the acute insulin response to glucose (AIRg) x the insulin sensitivity index (SI) in subjects during IVGTT on the 8th day (after 7 days) of on dex + placebo, then a after a washout of approximately 4 weeks, participants crossed over to dex + sitagliptin 100 mg x 7 days. Subjects were randomized to order of medication. The primary analyses will be an ANCOVA, including baseline responses as a covariate.
4 secondary outcomes
Change in Active GIP
Time frame: Active GIP would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GIP
Change in Active GLP-1
Time frame: Active GLP-1 would have been measured during MTT after 1 week of dex + sitagliptin and again after 1 week of dex + placebo, but we did not measure active GLP-1
Change in Glucose Response
Time frame: measured on day #9 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #9 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT
Change in Insulin Secretion (AIRg or Acute Insulinogenic Response to Glucose)
Time frame: measured twice: on day #8 (after 7 days of study drug and 1 day of IVGTT) of sitagliptin during MTT, then after 4 week washout, measured again on day #8 (after 7 days of study drug + 1 day of IVGTT) of dex + placebo during MTT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Annis M Marney, MD, MSCI principal investigator
University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexamethasone 2.5 mg and Sitagliptin 100 mg in people with Pre-diabetes and Impaired Fasting Glucose, run by University of Vermont 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 12 Mar 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Feb 2018). 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?
Insulin Sensitivity (time frame: Measured on day #8 (after 8 days of sitagliptin or placebo) followed by a 4 week washout then measured again on day #8 (after 8 days of crossover treatment).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2018.