Diabetes Mellitus, Type 2Phase 4NCT00656864
Pioglitazone Incretin Study
A Phase 4 study testing Pioglitazone in people with Diabetes Mellitus, Type 2, run by University of Vermont at 1 site in United States.
Trial summary
Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Nov 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes controlled with diet+exercise or metformin monotherapy
- HbA1c less than or equal to 7%
- Women will be non-fertile or practicing birth control
Who cannot join
- Acute or chronic medical conditions that would contraindicate participation
- Class III or IV heart failure
- Pregnant or nursing women
- Patients taking antidiabetic medications other than metformin, oral or chronic topical steroids, weight loss agents, antipsychotics, or other drugs that could affect insulin sensitivity or secretion.
- AST or ALT more than 2.5 times the upper limit of normal
- Active alcohol or drug abuse
- Weight greater than 300 pounds
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Vermont
South Burlington, Vermont, 05403
About this study
Official title: Effects of Pioglitazone on the Regulation of Insulin Secretion in Patients With Type 2 Diabetes
Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM) as in subjects who do not have diabetes. This study tests whether a medicine called pioglitazone (Actos), which is commonly used to treat T2DM, improves the ability of GIP to increase insulin secretion.
To address this question the investigators will recruit patients with T2DM whose diabetes is controlled with either diet and exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of studies to characterize their metabolism. These studies include an oral glucose tolerance test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion in response to glucose and GIP given through a vein. The investigators will also obtain small samples of fat (from just under the skin of the belly) using a needle to measure levels of the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with either pioglitazone or matching placebo (an inactive tablet that does not contain medication). The dose of pioglitazone will be increased during the first 4 weeks to the maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the treatment phase of the study. After 12 weeks of treatment all studies performed at the beginning of the study will be repeated. The pioglitazone treatment will continue until the end of testing, approximately 4 weeks.
The results of this study may give us information about why glucose control deteriorates in T2DM. This information might also lead to new ways to prevent or treat T2DM.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Pioglitazone, Placebo
- Keywords
- Diabetes, pioglitazone, GIP
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos (brand name for pioglitazone)
Starting dose at 15 mg for two weeks, then titrated up to 45 mg in the subsequent 2 weeks.
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Pioglitazone arm Receives: Drug: Pioglitazone |
| 2 | Placebo comparator | Placebo arm Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes.
Measured: 12 weeks per subject
Secondary outcomes (6)
Change in active GIP in response to an oral glucose tolerance test and mixed meal challenge
Measured: 12 weeks
Change in active GLP-1 in response to the oral glucose tolerance test and the mixed meal challenge
Measured: 12 weeks
Change in glucose response during the oral glucose tolerance test and mixed meal challenge
Measured: 12 weeks
Change in insulin secretion during the oral glucose tolerance test and the mixed meal challenge
Measured: 12 weeks
Change in the acute insulin response to glucose, insulin sensitivity and the disposition index during the IV glucose tolerance test.
Measured: 12 weeks
Change in adipocyte GIP receptor mRNA expression levels.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2008 (estimated)
- Study startMay 2008
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Investigators
- Richard E Pratley, MD, Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00656864
- Sponsor's protocol ID
- 08-107
- Other IDs
- GCRC-962
- Status last verified
- Jan 2010
- First submitted
- 7 Apr 2008
- Last updated
- 2 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Nunez Lopez YO, Casu A, Kovacova Z, Petrilli AM, Sideleva O, Tharp WG, Pratley RE. Coordinated regulation of gene expression and microRNA changes in adipose tissue and circulating extracellular vesicles in response to pioglitazone treatment in humans with type 2 diabetes. Front Endocrinol (Lausanne). 2022 Aug 31;13:955593. doi: 10.3389/fendo.2022.955593. eCollection 2022.
PubMed 36120427Tharp WG, Gupta D, Sideleva O, Deacon CF, Holst JJ, Elahi D, Pratley RE. Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide-Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes. Diabetes. 2020 Feb;69(2):146-157. doi: 10.2337/db18-1163. Epub 2019 Nov 22.
PubMed 31757794Kovacova Z, Tharp WG, Liu D, Wei W, Xie H, Collins S, Pratley RE. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring). 2016 Apr;24(4):820-8. doi: 10.1002/oby.21418. Epub 2016 Feb 17.
PubMed 26887289
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Pioglitazone on the Regulation of Insulin Secretion in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00656864
- Acronym / sponsor ID
- 08-107
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes, pioglitazone, GIP
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- May 2008
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 11 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. GLP-1 and GIP do not work as well in patients with type 2 diabetes (T2DM) as in subjects who do not have diabetes. This study tests whether a medicine called pioglitazone (Actos), which is commonly used to treat T2DM, improves the ability of GIP to increase insulin secretion.
To address this question the investigators will recruit patients with T2DM whose diabetes is controlled with either diet and exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat by DEXA scanning and a series of studies to characterize their metabolism. These studies include an oral glucose tolerance test (a test sometimes used to diagnose diabetes), a mixed-meal challenge (to measure how much GLP-1 and GIP are produced in response to a meal) and measurement of insulin secretion in response to glucose and GIP given through a vein. The investigators will also obtain small samples of fat (from just under the skin of the belly) using a needle to measure levels of the receptor for GIP. Subjects will then be randomly assigned to 12 weeks of treatment with either pioglitazone or matching placebo (an inactive tablet that does not contain medication). The dose of pioglitazone will be increased during the first 4 weeks to the maximum prescribed dose of 45 mg per day. Subjects will be seen every 2-4 weeks during the treatment phase of the study. After 12 weeks of treatment all studies performed at the beginning of the study will be repeated. The pioglitazone treatment will continue until the end of testing, approximately 4 weeks.
The results of this study may give us information about why glucose control deteriorates in T2DM. This information might also lead to new ways to prevent or treat T2DM.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: PioglitazonePioglitazone arm |
| 2 | Placebo comparator | Drug: PlaceboPlacebo arm |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Type 2 diabetes controlled with diet+exercise or metformin monotherapy
- HbA1c less than or equal to 7%
- Women will be non-fertile or practicing birth control
Key exclusion criteria (7 listed)
- Acute or chronic medical conditions that would contraindicate participation
- Class III or IV heart failure
- Pregnant or nursing women
- Patients taking antidiabetic medications other than metformin, oral or chronic topical steroids, weight loss agents, antipsychotics, or other drugs that could affect insulin sensitivity or secretion.
- AST or ALT more than 2.5 times the upper limit of normal
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 |
|---|---|---|
| PioglitazoneAlso: Actos (brand name for pioglitazone)Starting dose at 15 mg for two weeks, then titrated up to 45 mg in the subsequent 2 weeks. | Drug | 1 |
| Placeboplacebo | Drug | 2 |
Primary outcome
Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes.
Time frame: 12 weeks per subject
6 secondary outcomes
Change in active GIP in response to an oral glucose tolerance test and mixed meal challenge
Time frame: 12 weeks
Change in active GLP-1 in response to the oral glucose tolerance test and the mixed meal challenge
Time frame: 12 weeks
Change in glucose response during the oral glucose tolerance test and mixed meal challenge
Time frame: 12 weeks
Change in insulin secretion during the oral glucose tolerance test and the mixed meal challenge
Time frame: 12 weeks
Change in the acute insulin response to glucose, insulin sensitivity and the disposition index during the IV glucose tolerance test.
Time frame: 12 weeks
Change in adipocyte GIP receptor mRNA expression levels.
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2011.
- Derived from this study: PubMed 36120427Nunez Lopez YO, Casu A, Kovacova Z, Petrilli AM, Sideleva O, Tharp WG, Pratley RE. Coordinated regulation of gene expression and microRNA changes in adipose tissue and circulating extracellular vesicles in response to pioglitazone treatment in humans with type 2 diabetes. Front Endocrinol (Lausanne). 2022 Aug 31;13:955593. doi: 10.3389/fendo.2022.955593. eCollection 2022.
- Derived from this study: PubMed 31757794Tharp WG, Gupta D, Sideleva O, Deacon CF, Holst JJ, Elahi D, Pratley RE. Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide-Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes. Diabetes. 2020 Feb;69(2):146-157. doi: 10.2337/db18-1163. Epub 2019 Nov 22.
- Derived from this study: PubMed 26887289Kovacova Z, Tharp WG, Liu D, Wei W, Xie H, Collins S, Pratley RE. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring). 2016 Apr;24(4):820-8. doi: 10.1002/oby.21418. Epub 2016 Feb 17.
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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.
Richard E Pratley, MD 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 Phase 4 study testing Pioglitazone in people with Diabetes Mellitus, Type 2, 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 7 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 2 Feb 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in incretin-mediated insulin secretion and receptor regulation of glucose-dependent insulinotropic peptide (GIP) in patients with type 2 diabetes. (time frame: 12 weeks per subject). 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 NCT00656864, which also lists 3 linked publications.
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 2 Feb 2011.