Type 2 DiabetesPhase 4PIO-EXNCT00845182

Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function

A Phase 4 study testing Pioglitazone, Exenatide and Pioglitazone and Exenatide in people with Type 2 Diabetes and Healthy, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes, Healthy, Impaired Glucose Tolerance
What is being tested?: Pioglitazone, Exenatide and Pioglitazone and Exenatide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 1 siteUnited States
Study dates: Jun 2007to Jul 2010
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 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Diabetic patients must be on diet therapy alone or diet plus a sulfonylurea, or diet plus metformin, or diet plus sulfonylurea/metformin and have a HbA1c ≥ 7.0%.
Patients must have the following laboratory values:
Hematocrit ≥ 34 vol% Serum creatinine ≤ 1.8 mg/dl AST (SGOT) ≤ 2 times upper limit of normal ALT (SGPT) ≤ 2 times upper limit of normal Alkaline phosphatase ≤ 2 times upper limit of normal
Patients must have been on a stable dose of allowed chronic medications for 30 days prior to entering the study.
Body weight must be stable (± 3-4 pounds) over the three months prior to study
The normal healthy control group will be age, weight (BMI), and gender matched with the diabetic group and must have a normal OGTT according to ADA criteria.
Subjects with IFG/IGT will have a FPG (100-125mg/dl) and/or 2-h plasma glucose (140-199mg/dl) according to ADA criteria.

Who cannot join

Patients must not have type 1 diabetes.
Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c > 10.0%.
Patients must not have received a thiazolidinedione or insulin for more than one week during the year prior to randomization.
Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2.

Trial locations and contacts

1 site in 1 country.

United States1 site

Barter Research Center, ALM VA Hospital
San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Effect of Pioglitazone With and Without Exenatide on Body Weight, Fat Topography, Beta Cell Function, and Glycemic Control in Type 2 Diabetic Patients

Pioglitazone, a drug used in treatment of type 2 diabetes has been shown to improve insulin sensitivity in skeletal muscle, liver, and fat cells. Despite the beneficial effects of pioglitazone to improve insulin sensitivity and reduce cardiovascular disease in high risk type 2 diabetic patients, weight gain has been a limiting factor. Exenatide, another agent used for treatment of T2DM, improves glycemic control and promotes moderate weight loss. In this proposal we will examine the effect of combination therapy with pioglitazone plus exenatide on body weight, fat topography, beta cell function, glycemic control, and plasma lipid levels in subjects with type 2 diabetes mellitus compared to treatment with each drug separately. Assessment of beta cell function will be performed by measuring the maximal insulin secretory capacity using a maximal hyperglycemic stimulus combined with an intravenous arginine stimulus.

Read the detailed description

The thiazolidinedione (TZD) class of drugs has been shown to improve insulin sensitivity in skeletal muscle, liver, and adipocytes and to have anti-inflammatory and cardioprotective effects. The beta cell function, measured by the insulin secretion/insulin resistance index during the OGTT, improves significantly. In the present study, we will perform a more definitive assessment of beta cell function in TZD-treated diabetic patients by measuring the maximal insulin secretory capacity using a maximal hyperglycemic stimulus combined with an intravenous arginine stimulus.

Despite the beneficial effects of pioglitazone to improve insulin sensitivity and reduce cardiovascular events in high risk type 2 diabetic patients, weight gain has been a limiting factor for primary care physicians even though pioglitazone treatment leads to a redistribution of fat out of muscle/liver/visceral area to subcutaneous fat.

Exenatide (Byetta) is 39 amino acid peptide which exhibits biological actions similar to GLP-1. In clinical trials exenatide reduces HbA1c by 1-1.2% in subjects with type 2 diabetes and promotes moderate weight loss which is sustained for up to 2 years.

In this proposal we will examine the effect of combination therapy with pioglitazone plus exenatide on body weight, fat topography, beta cell function, glycemic control, and plasma lipid levels in subjects with type 2 diabetes mellitus compared to monotherapy with each agent separately. We postulate that combination therapy will result in significant weight loss (in contrast to the weight gain which accompanies pioglitazone treatment) and have an additive, or even synergistic, effect to improve beta cell function and glycemic control in type 2 diabetic patients who are inadequately controlled on oral agent therapy with metformin alone, a sulfonylurea alone, or combination of metformin plus a sulfonylurea. We will also compare the insulin secretion in healthy control subjects (NGT, n=15) and subjects with impaired glucose tolerance (IGT, n=15) to evaluate the relative decline in beta cell function in T2DM compared to NGT and IGT subjects. NGT and IGT subjects will participate only in a OGTT and a Hyperglycemic clamp- they will not receive any medication.

Conditions: Type 2 Diabetes, Healthy, Impaired Glucose Tolerance
Being tested: Pioglitazone, Exenatide, Pioglitazone and Exenatide
Keywords: Type 2 diabetes pathogenesis, thiazolidinediones, impaired glucose tolerance, Incretins, Insulin secretion
Medical subject headings: Diabetes Mellitus, Type 2, Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PioglitazoneDrug
Also called ACTOS
Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months
ExenatideDrug
Also called BYETTA
Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months
Pioglitazone and ExenatideDrug
Also called ACTOS, BYETTA
Pioglitazone 30mg daily for 1 month and then 45mg daily for 5 months and Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months

Study groups in NCT00845182
Study group	Role	What they receive
Pioglitazone	Active comparator	Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm Receives: Drug: Pioglitazone
Exenatide	Experimental	Exenatide: 15 subjects will be randomized to receive Exenatide Receives: Drug: Exenatide
Drug Pioglitazone and Drug Exentatide	Experimental	Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide Receives: Drug: Pioglitazone and Exenatide

What is being measured

The primary outcome is the main question the study is designed to answer.

Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight
Effect of Pioglitazone, Exenatide and combined Pioglitazone and Exenatide on body weight and beta cell function
Measured: baseline and 6 months
HbA1c
change in HbA1c was measured before and after treatment in three groups
Measured: baseline and 6 months

Secondary outcomes (1)

Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatide • Insulin Sensitivity • Inflammatory Cytokines • Glucagon and Free Fatty Acids • Plasma Lipids
Effect pioglitazone, exenatide, and pioglitazone plus exenatide on
- Insulin sensitivity
- Inflammatory cytokines
- glucagon and free fatty acids
- plasma lipids measured over a 6 month period
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Jul 2010

First posted18 Feb 2009 (estimated)
Study startJun 2007
Primary completionJul 2010
Study completionJul 2010

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 Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by The University of Texas Health Science Center at San AntonioThe 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: Single blind
Who is masked: Participant
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00845182
Sponsor's protocol ID: HSC2007243H
Acronym: PIO-EX
Status last verified: May 2017
First submitted: 17 Feb 2009
Last updated: 18 Jan 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Guardado-Mendoza R, Chavez AO, Jimenez-Ceja LM, Hansis-Diarte A, DeFronzo RA, Folli F, Tripathy D. Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus. Acta Diabetol. 2017 Jan;54(1):53-61. doi: 10.1007/s00592-016-0904-7. Epub 2016 Sep 13.
PubMed 27624579

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Pioglitazone With and Without Exenatide on Body Weight, Fat Topography, Beta Cell Function, and Glycemic Control in Type 2 Diabetic Patients
ClinicalTrials.gov ID: NCT00845182
Acronym / sponsor ID: PIO-EX / HSC2007243H
Conditions: Type 2 Diabetes, Healthy, Impaired Glucose Tolerance
Keywords: Type 2 diabetes pathogenesis, thiazolidinediones, impaired glucose tolerance, Incretins, Insulin secretion
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 43 participants (actual)
Lead sponsor: The University of Texas Health Science Center at San AntonioUniversity, hospital or other
Study start: Jun 2007
Primary completion: Jul 2010 (actual)
Study completion: Jul 2010 (actual)
First posted: 18 Feb 2009 (estimated)
Results: Posted 17 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 3

Arm	Type	Receives
Pioglitazone	Active comparator	Drug: PioglitazonePioglitazone: 15 Patients will be randomized to Pioglitazone only arm
Exenatide	Experimental	Drug: ExenatideExenatide: 15 subjects will be randomized to receive Exenatide
Drug Pioglitazone and Drug Exentatide	Experimental	Drug: Pioglitazone and ExenatidePioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Diabetic patients must be on diet therapy alone or diet plus a sulfonylurea, or diet plus metformin, or diet plus sulfonylurea/metformin and have a HbA1c ≥ 7.0%.
Patients must have the following laboratory values:
Hematocrit ≥ 34 vol% Serum creatinine ≤ 1.8 mg/dl AST (SGOT) ≤ 2 times upper limit of normal ALT (SGPT) ≤ 2 times upper limit of normal Alkaline phosphatase ≤ 2 times upper limit of normal
Patients must have been on a stable dose of allowed chronic medications for 30 days prior to entering the study.
Body weight must be stable (± 3-4 pounds) over the three months prior to study

Key exclusion criteria (4 listed)

Patients must not have type 1 diabetes.
Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c > 10.0%.
Patients must not have received a thiazolidinedione or insulin for more than one week during the year prior to randomization.
Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2.

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: ACTOSPioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months	Drug	Pioglitazone
ExenatideAlso: BYETTAExenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months	Drug	Exenatide
Pioglitazone and ExenatideAlso: ACTOS, BYETTAPioglitazone 30mg daily for 1 month and then 45mg daily for 5 months and Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months	Drug	Drug Pioglitazone and Drug Exentatide

Primary outcome

Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight
Time frame: baseline and 6 months
Effect of Pioglitazone, Exenatide and combined Pioglitazone and Exenatide on body weight and beta cell function
HbA1c
Time frame: baseline and 6 months
change in HbA1c was measured before and after treatment in three groups

1 secondary outcome

Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatide • Insulin Sensitivity • Inflammatory Cytokines • Glucagon and Free Fatty Acids • Plasma Lipids
Time frame: 6 months

Results and safety

Results posted to the registry on 17 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pioglitazone	13	10
Exenatide	15	11
Pioglitazone and Exentatide	15	9

Primary outcome: Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight

Time frame: baseline and 6 months. Mean (Standard Deviation). Unit: kg

Measure	PIOGLITAZONE n = 10	EXENATIDE n = 11	PIOGLITAZONE and EXNATIDE n = 9
Value	5.5 (7.3)	2.4 (2.8)	2.7 (4.4)

PIOGLITAZONE vs EXENATIDE vs PIOGLITAZONE and EXNATIDE: p <0.05, ANCOVA
PIOGLITAZONE vs EXENATIDE vs PIOGLITAZONE and EXNATIDE: p <0.05, ANOVA

Population analysed: we analyzed the weight at the end of study completion

Primary outcome: HbA1c

Time frame: baseline and 6 months. Mean (Standard Deviation). Unit: percent point decrease from baseline

Measure	Pioglitazone n = 10	Exenatide n = 11	Drug Pioglitazone and Drug Exentatide n = 9
Value	1.37 (0.68)	1.09 (0.68)	1.91 (1.20)

Population analysed: There was a greater improvement in HbA1c from baseline after combined treatment with Pioglitazone and Exenatide when compared with either therapy alone.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Patients were followed for 6 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pioglitazone	0 of 12 (0%)	2 of 12 (16.7%)	Not reported
Exenatide	0 of 15 (0%)	1 of 15 (6.7%)	Not reported
Pioglitazone and Exentatide	0 of 15 (0%)	1 of 15 (6.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27624579Guardado-Mendoza R, Chavez AO, Jimenez-Ceja LM, Hansis-Diarte A, DeFronzo RA, Folli F, Tripathy D. Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus. Acta Diabetol. 2017 Jan;54(1):53-61. doi: 10.1007/s00592-016-0904-7. Epub 2016 Sep 13.

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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.

Devjit Tripathy, MD principal investigator

The University of Texas Health Science Center at San Antonio

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 7 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 18 Jan 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. 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 17 Mar 2015). 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?

Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight (time frame: baseline and 6 months). The study lists 2 primary outcomes in all. 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 NCT00845182, 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 18 Jan 2018.