Type 2 Diabetes MellitusPhase 4NCT00179400
The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
A Phase 4 study testing Pioglitazone and Pancreatic Clamp Study in people with Type 2 Diabetes Mellitus, run by Albert Einstein College of Medicine at 1 site in United States.
Trial summary
The purpose of this study is to investigate the acute effects of the thiazolidinedione agent pioglitazone (which has combined PPAR alpha and gamma stimulation) on insulin's ability to suppress glucose production, stimulated glucose uptake, and impact a number of other metabolically important endpoints, including… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Pioglitazone and Pancreatic Clamp Study
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Jul 2011
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals with Type 2 Diabetes
Who cannot join
- Individuals with bleeding disorders including gastrointestinal reflux disease (GERD), peptic ulcer disease (PUD), any gastrointestinal (GI) bleeding
- High blood pressure
- History of Coronary Artery Disease or chest pain on exertion
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: The Role of Acute Combined Peroxisome Proliferator-Activated Receptors (PPAR) Alpha and Gamma Stimulation on Insulin Action in Humans
The purpose of this study is to investigate the acute effects of the thiazolidinedione agent pioglitazone (which has combined PPAR alpha and gamma stimulation) on insulin's ability to suppress glucose production, stimulated glucose uptake, and impact a number of other metabolically important endpoints, including production of adiponectin (a protein hormone which regulates sugar levels and fatty acid breakdown) in subjects with type 2 diabetes.
Read the detailed description
Participants in this study were given a supply of either pioglitazone (a medication used to treat diabetes) or matched placebo for a duration of 10 days or 21 days. Changes to the body's response to insulin in the liver and in peripheral tissues (eg, muscle and fat) will be measured using a procedure called a pancreatic clamp. During the clamp procedure, glucose (a sugar) and insulin were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Small amounts of muscle and fat tissue were also taken during this study to measure changes in gene expression after taking the medication/placebo.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Pioglitazone, Placebo, Pancreatic Clamp Study
- Keywords
- Type 2 Diabetes Mellitus
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos, Thiazolidinedione
This was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study.
PlaceboDrug
Also called Control
This was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study.
Pancreatic Clamp StudyProcedure or surgery
Also called Glucose clamp technique
During the clamp procedure, glucose (a sugar) and insulin were infused with an IV catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | Participants received Pioglitazone 45 mg via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period.
The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. Receives: Drug: Pioglitazone; Procedure: Pancreatic Clamp Study |
| Placebo | Placebo comparator | Participants received matched placebo via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period.
The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. Receives: Drug: Placebo; Procedure: Pancreatic Clamp Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endogenous Glucose Production (EGP)
EGP (a measure of the body's production of sugar) was measured by using a 6-hour stepped pancreatic clamp procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days), by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). The relevant data at the end of each last 60 minute bin of each run was reported for each of the four groups up to 6 hours. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Measured: Up to 6 hours
Glucose Rates of Disappearance (Rd)
Glucose rates of disappearance were measured using a stepped pancreatic clamp study procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days) by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). For purposes of this study, the most relevant data for the final hour is summarized within each study Pioglitazone and Placebo study arm/group, respectively. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Measured: Up to 6 hours
Secondary outcomes (4)
Gene Expression in Both Whole Fat Tissue and Isolated Macrophages
Gene expression of inflammatory markers in both whole fat tissue and isolated macrophages were studied by quantitative, real-time reverse transcriptase polymerase chain reaction (RT-PCR) in placebo and Pioglitazone groups of either 10- or 21-day study. The reporting data was calculated as the ratio between the target genes and housekeeping genes in either the 10- or 21-day study.
Measured: Outcome was compared prior to and post 10-day or 21-day administration of either placebo or Pioglitazone
Effects of Pioglitazone on Adipose Tissue Percentage of Macrophage Content
Adipose tissue biopsy was performed on day one or on the last day (10th or 21st day) for the corresponding Pioglitazone and placebo interventions. Macrophages were stained with immunofluorescence antibody after isolation from adipose tissue and processed. The percentage of macrophage content in stromal vascular fraction cells (SVF) analyzed by Fluorescence-activated cell sorter analysis (FACS) was determined. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Measured: Assessed at day 1 prior to the intervention and on day 10 or 21 following the intervention, day 10 or 21 following the intervention reported
Adipose Tissue Percentage of Macrophage Content
Adipose tissue percentage of macrophage content was analyzed by Immuno-fluorescence staining (iNOS+ and CD68+). Both the immuno-fluorescence stained macrophages and all other stained cells will be counted after staining. The percentage of macrophage content will be calculated as the the ratio between the number of macrophage and all other cells.
Measured: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration
Adipose Tissue Regulatory T Lymphocyte Content
Adipose tissue T lymphocyte content (%) was analyzed by Immunohistochemistry (IHC) staining with Treg-specific marker FOXP3
Both the IHC FOXP3 stained T lymphocyte and all other stained cells will be counted after staining. The percentage of T lymphocyte content will be calculated as the the ratio between the number of T lymphocyte and all other cells.
Measured: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startDec 2000
- Primary completionJul 2011
- Study completionJul 2011
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 Type 2 Diabetes MellitusStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Principal investigator, Meredith Hawkins, Albert Einstein College of Medicine
- Investigators
- Meredith Hawkins, M.D., M.S., Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00179400
- Sponsor's protocol ID
- 2000-200
- Status last verified
- Feb 2025
- First submitted
- 13 Sep 2005
- Last updated
- 3 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Acute Combined Peroxisome Proliferator-Activated Receptors (PPAR) Alpha and Gamma Stimulation on Insulin Action in Humans
- ClinicalTrials.gov ID
- NCT00179400
- Acronym / sponsor ID
- 2000-200
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Dec 2000 (actual)
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 3 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the acute effects of the thiazolidinedione agent pioglitazone (which has combined PPAR alpha and gamma stimulation) on insulin's ability to suppress glucose production, stimulated glucose uptake, and impact a number of other metabolically important endpoints, including production of adiponectin (a protein hormone which regulates sugar levels and fatty acid breakdown) in subjects with type 2 diabetes.
Detailed description
Participants in this study were given a supply of either pioglitazone (a medication used to treat diabetes) or matched placebo for a duration of 10 days or 21 days. Changes to the body's response to insulin in the liver and in peripheral tissues (eg, muscle and fat) will be measured using a procedure called a pancreatic clamp. During the clamp procedure, glucose (a sugar) and insulin were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Small amounts of muscle and fat tissue were also taken during this study to measure changes in gene expression after taking the medication/placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: Pioglitazone, Procedure: Pancreatic Clamp StudyParticipants received Pioglitazone 45 mg via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. |
| Placebo | Placebo comparator | Drug: Placebo, Procedure: Pancreatic Clamp StudyParticipants received matched placebo via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Individuals with Type 2 Diabetes
Key exclusion criteria (3 listed)
- Individuals with bleeding disorders including gastrointestinal reflux disease (GERD), peptic ulcer disease (PUD), any gastrointestinal (GI) bleeding
- High blood pressure
- History of Coronary Artery Disease or chest pain on exertion
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, ThiazolidinedioneThis was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study. | Drug | Pioglitazone |
| PlaceboAlso: ControlThis was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study. | Drug | Placebo |
| Pancreatic Clamp StudyAlso: Glucose clamp techniqueDuring the clamp procedure, glucose (a sugar) and insulin were infused with an IV catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. | Procedure or surgery | Pioglitazone, Placebo |
Primary outcome
Endogenous Glucose Production (EGP)
Time frame: Up to 6 hours
EGP (a measure of the body's production of sugar) was measured by using a 6-hour stepped pancreatic clamp procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days), by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). The relevant data at the end of each last 60 minute bin of each run was reported for each of the four groups up to 6 hours. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Glucose Rates of Disappearance (Rd)
Time frame: Up to 6 hours
Glucose rates of disappearance were measured using a stepped pancreatic clamp study procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days) by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). For purposes of this study, the most relevant data for the final hour is summarized within each study Pioglitazone and Placebo study arm/group, respectively. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
4 secondary outcomes
Gene Expression in Both Whole Fat Tissue and Isolated Macrophages
Time frame: Outcome was compared prior to and post 10-day or 21-day administration of either placebo or Pioglitazone
Effects of Pioglitazone on Adipose Tissue Percentage of Macrophage Content
Time frame: Assessed at day 1 prior to the intervention and on day 10 or 21 following the intervention, day 10 or 21 following the intervention reported
Adipose Tissue Percentage of Macrophage Content
Time frame: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration
Adipose Tissue Regulatory T Lymphocyte Content
Time frame: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Meredith Hawkins, M.D., M.S. principal investigator
Albert Einstein College of Medicine
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 and Pancreatic Clamp Study in people with Type 2 Diabetes Mellitus, run by Albert Einstein College of Medicine 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 1 inclusion and 3 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 3 Mar 2025. 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 3 Mar 2025). 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?
Endogenous Glucose Production (EGP) (time frame: Up to 6 hours). 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?
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 3 Mar 2025.