Type 2 Diabetes MellitusPhase 4NCT01432405
Effect Of Exenatide Treatment on Liver Fat Content in Patients With Diabetes
A Phase 4 study testing Exenatide and Pioglitazone in people with Type 2 Diabetes Mellitus, run by Baylor College of Medicine at 1 site in United States.
Trial summary
The purpose of this study is to examine the effect of exenatide, an anti-diabetes medication, on liver fat and blood levels of proteins that influence liver fat. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Exenatide and Pioglitazone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Jun 2009
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must range in age from 30 to 70 years.
- Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Patients may be of either sex. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions or be surgically sterilized.
- Patients must meet the American Diabetes Association Criteria for diagnosis of type 2 diabetes mellitus.
- Patients must be on diet therapy alone and/or metformin treatment (stable dose) and have a fasting plasma glucose concentration between 126 and 260 mg/dl.
- Patients must have Hematocrit greater than 34%.
- Subjects whose body weight has been stable (±1 Kg) over the three months prior to study will be included.
Who cannot join
- 1, Type 1 diabetes.
- 2. Fasting plasma glucose greater than 260 mg/dl.
- 3. Patients must not have received a thiazolidinedione for at least 3 months prior to randomization.
- 4. Patients must not be on insulin treatment or have received insulin for more than one week within the previous year prior to entry. Patients should not be on sulfonylureas, sitagliptin, or exenatide treatment.
- 5. Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded.
- 6. Patients taking medications that affect gastrointestinal motility will be excluded
- 7. Patients with a history of Congestive Heart failure (CHF), or clinically significant cardiac, liver or kidney disease (creatinine greater than 1.8 mg/dl).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Exenatide Treatment on Hepatic Fat Content and Plasma Adipocytokine Levels in Patients With Type 2 Diabetes Mellitus
The purpose of this study is to examine the effect of exenatide, an anti-diabetes medication, on liver fat and blood levels of proteins that influence liver fat.
Read the detailed description
Obesity is characterized as generalized expansion of all adipose tissue depots, an increase in tissue lipid content, and dyslipidemia, insulin resistance, and type 2 diabetes. The adipocyte functions not only as a storage depot for fat but as an endocrine organ that releases hormones in response to specific extracellular stimuli or changes in metabolic status. These secreted proteins, carry out a variety of diverse functions, and they have been referred to collectively as adipokines. The adipokines have been postulated to play important roles in the pathogenesis of insulin resistance, hypertension, disorders of coagulation, dyslipidemia, and glucose intolerance, abnormalities associated with insulin resistance syndrome.
These observations are of considerable interest because recent studies have provided evidence that increased hepatic fat content is an important determinant of hepatic insulin resistance in type 2 diabetic patients. Fatty liver is common in type 2 diabetic patients. The mechanisms responsible for the increase in hepatic fat content are unclear. It has been suggested that fatty liver results from accelerated fatty acid mobilization from expanded visceral fat stores and their deposition in the liver as well as decreased hepatic fatty acid oxidation. Weight loss in humans with Non Alcoholic Fatty Liver Disease (NAFLD) is associated with a decrease in hepatic fat content. In addition, thiazolidinediones have been shown to reduce hepatic fat content and improve hepatic insulin sensitivity in patients with type 2 diabetes as well as in non-diabetic patients with NAFLD. The thiazolidinediones initiate their action by binding the peroxisome proliferator activator receptors (PPAR) , which primarily are located on adipocytes. Treatment of insulin-resistant mice as well as type 2 diabetic patients with insulin sensitizing PPAR activators, such as thiazolidinediones, and increases plasma adiponectin levels. Indirect evidence suggests that adiponectin might mediate some of the insulin-sensitizing effects of PPAR agonists.
Exenatide, a Glucagon Like Peptide-1 (GLP-1) receptor agonist approved for treatment of type 2 diabetes, elicited dose-dependent reductions in body weight in association with improved glycemic control in type 2 diabetic patients. In animal models of obesity, exenatide reduces hepatic fat. However, the effect of exenatide treatment in combination with a thiazolidinedione on liver fat content and plasma adipocytokines levels in patients with type 2 diabetes remains to be investigated.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Exenatide, Pioglitazone
- Keywords
- Diabetes
- 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.
ExenatideDrug
Also called Byetta
Type 2 diabetic subjects will be randomized to receive exenatide 10 micrograms injected subcutaneously twice daily for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period.
PioglitazoneDrug
Also called Actos
Type 2 diabetic subjects will be randomized to receive pioglitazone 45 mg daily orally for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone and exenatide | Experimental | Exenatide 10 micrograms injected subcutaneously twice daily plus pioglitazone 45 mg daily orally for 12 months. Receives: Drug: Exenatide; Drug: Pioglitazone |
| Pioglitazone | Experimental | Pioglitazone 45 mg daily orally for 12 months Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Fat
The effect of exenatide and pioglitazone on liver fat content after one year of treatment in patients with type 2 diabetes.
Measured: one year
Secondary outcomes (1)
Plasma Adipocytokines
the effect of the intervention on plasma adiponectin levels.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study startJun 2007
- Primary completionJul 2008
- Study completionJun 2009
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 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mandeep Bajaj, Baylor College of Medicine
- Investigators
- Mandeep Bajaj, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01432405
- Sponsor's protocol ID
- H-21068
- Status last verified
- Mar 2016
- First submitted
- 9 Sep 2011
- Last updated
- 12 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Samson SL, Sathyanarayana P, Jogi M, Gonzalez EV, Gutierrez A, Krishnamurthy R, Muthupillai R, Chan L, Bajaj M. Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. Diabetologia. 2011 Dec;54(12):3093-100. doi: 10.1007/s00125-011-2317-z. Epub 2011 Sep 29.
PubMed 21956711
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Exenatide Treatment on Hepatic Fat Content and Plasma Adipocytokine Levels in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01432405
- Acronym / sponsor ID
- H-21068
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Posted 12 Apr 2016
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 examine the effect of exenatide, an anti-diabetes medication, on liver fat and blood levels of proteins that influence liver fat.
Detailed description
Obesity is characterized as generalized expansion of all adipose tissue depots, an increase in tissue lipid content, and dyslipidemia, insulin resistance, and type 2 diabetes. The adipocyte functions not only as a storage depot for fat but as an endocrine organ that releases hormones in response to specific extracellular stimuli or changes in metabolic status. These secreted proteins, carry out a variety of diverse functions, and they have been referred to collectively as adipokines. The adipokines have been postulated to play important roles in the pathogenesis of insulin resistance, hypertension, disorders of coagulation, dyslipidemia, and glucose intolerance, abnormalities associated with insulin resistance syndrome.
These observations are of considerable interest because recent studies have provided evidence that increased hepatic fat content is an important determinant of hepatic insulin resistance in type 2 diabetic patients. Fatty liver is common in type 2 diabetic patients. The mechanisms responsible for the increase in hepatic fat content are unclear. It has been suggested that fatty liver results from accelerated fatty acid mobilization from expanded visceral fat stores and their deposition in the liver as well as decreased hepatic fatty acid oxidation. Weight loss in humans with Non Alcoholic Fatty Liver Disease (NAFLD) is associated with a decrease in hepatic fat content. In addition, thiazolidinediones have been shown to reduce hepatic fat content and improve hepatic insulin sensitivity in patients with type 2 diabetes as well as in non-diabetic patients with NAFLD. The thiazolidinediones initiate their action by binding the peroxisome proliferator activator receptors (PPAR) , which primarily are located on adipocytes. Treatment of insulin-resistant mice as well as type 2 diabetic patients with insulin sensitizing PPAR activators, such as thiazolidinediones, and increases plasma adiponectin levels. Indirect evidence suggests that adiponectin might mediate some of the insulin-sensitizing effects of PPAR agonists.
Exenatide, a Glucagon Like Peptide-1 (GLP-1) receptor agonist approved for treatment of type 2 diabetes, elicited dose-dependent reductions in body weight in association with improved glycemic control in type 2 diabetic patients. In animal models of obesity, exenatide reduces hepatic fat. However, the effect of exenatide treatment in combination with a thiazolidinedione on liver fat content and plasma adipocytokines levels in patients with type 2 diabetes remains to be investigated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone and exenatide | Experimental | Drug: Exenatide, Drug: PioglitazoneExenatide 10 micrograms injected subcutaneously twice daily plus pioglitazone 45 mg daily orally for 12 months. |
| Pioglitazone | Experimental | Drug: PioglitazonePioglitazone 45 mg daily orally for 12 months |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must range in age from 30 to 70 years.
- Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Patients may be of either sex. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions or be surgically sterilized.
- Patients must meet the American Diabetes Association Criteria for diagnosis of type 2 diabetes mellitus.
- Patients must be on diet therapy alone and/or metformin treatment (stable dose) and have a fasting plasma glucose concentration between 126 and 260 mg/dl.
Key exclusion criteria (7 listed)
- 1, Type 1 diabetes.
- 2. Fasting plasma glucose greater than 260 mg/dl.
- 3. Patients must not have received a thiazolidinedione for at least 3 months prior to randomization.
- 4. Patients must not be on insulin treatment or have received insulin for more than one week within the previous year prior to entry. Patients should not be on sulfonylureas, sitagliptin, or exenatide treatment.
- 5. Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded.
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 |
|---|---|---|
| ExenatideAlso: ByettaType 2 diabetic subjects will be randomized to receive exenatide 10 micrograms injected subcutaneously twice daily for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period. | Drug | Pioglitazone and exenatide |
| PioglitazoneAlso: ActosType 2 diabetic subjects will be randomized to receive pioglitazone 45 mg daily orally for 12 months. Prior to randomization, all subjects will receive baseline measurements of fasting plasma glucose, plasma adipocytokines, Free Fatty Acids, insulin, plasma lipids, and HbA1c as well as measurement of liver fat content with magnetic resonance spectroscopy. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, insulin and adipocytokines as well as hepatic fat content determination at the end of the 12 month treatment period. | Drug | Pioglitazone, Pioglitazone and exenatide |
Primary outcome
Hepatic Fat
Time frame: one year
The effect of exenatide and pioglitazone on liver fat content after one year of treatment in patients with type 2 diabetes.
1 secondary outcome
Plasma Adipocytokines
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21956711Samson SL, Sathyanarayana P, Jogi M, Gonzalez EV, Gutierrez A, Krishnamurthy R, Muthupillai R, Chan L, Bajaj M. Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. Diabetologia. 2011 Dec;54(12):3093-100. doi: 10.1007/s00125-011-2317-z. Epub 2011 Sep 29.
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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.
Mandeep Bajaj, MD principal investigator
Baylor 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 Exenatide and Pioglitazone in people with Type 2 Diabetes Mellitus, run by Baylor 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 7 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 12 Apr 2016. 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 12 Apr 2016). 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?
Hepatic Fat (time frame: one year). 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 NCT01432405, 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 12 Apr 2016.