Diabetes MellitusPhase 2NCT00064714
Effect of AC2993 With or Without Immunosuppression on Beta Cell Function in Patients With Type I Diabetes
A Phase 2 study testing AC2993 (exenatide) and daclizumab (immunosuppressive) in people with Diabetes Mellitus, run by AstraZeneca at 1 site in United States.
Trial summary
This study will determine 1) the safety of AC2993 in patients with type I diabetes; 2) the ability of AC2993 to improve beta cell function; and 3) the effects of immunosuppression on beta cell function. Type I diabetes is an autoimmune disease, in which the immune system attacks the beta cells of the pancreas. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- AC2993 (exenatide) and daclizumab (immunosuppressive)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to Mar 2008
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- T1DM for at least 5 years as defined by the following:
- Insulin dependence (with an insulin requirement less than 0.8 units/kg/day).
- Current or past anti-islet antibodies (anti-insulin before initiation of insulin therapy, anti-islet cell (ICA), anti-tyrosine phosphatase IA-2, and/or anti-glutamic acid decarboxylase (GAD65) antibodies).
- BMI greater than or equal to 20 kg/m(2) and less than or equal to 30 kg/m(2).
- C-peptide greater than or equal to 0.3 and less than or equal to 1.2 ng/mL at baseline or during an arginine-stimulated C-peptide test.
- Age 18 to 60 years, inclusive.
Who cannot join
- Symptomatic gastroparesis.
- Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24-hour urine albumin greater than 300 mg.
- Insulin requirements greater than 0.8 units/kg/day.
- Hypoglycemia unawareness: Unless easily corrected via simple modifications in the patient's diabetes regimen, the potential enrollee will be excluded if he/she has suffered greater than or equal to 2 episodes of severe hypoglycemia during the most recent 12 months, defined as requiring assistance from a third party, receiving assistance from medics, visiting an ER or being hospitalized due to the hypoglycemia.
- Evidence of chronic infection.
- History of any malignancy.
Show all 14Show fewer
- Any chronic medical condition that unduly increase risk for the potential enrollee as judged by study investigators.
- Hematologic abnormalities:
- Anemia (hematocrit less than 31.8% in women and less than 36.7% in men).
- Leukopenia (WBC count less than 3.4 K/mm(3)).
- Thrombocytopenia (platelet count less than 162 K/mm(3)).
- Hypertension, whether untreated or resistant to medical treatment, with blood pressure greater than 140/85 mm Hg.
- Pregnancy, breastfeeding or planned pregnancy within two years.
- Unable to identify primary care provider willing to partner with study investigators.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effect of AC 2993 (Synthetic Exendin-4) - Administered Alone or in Combination With Daclizumab - on Islet Function in Patients With Type I Diabetes
This study will determine 1) the safety of AC2993 in patients with type I diabetes; 2) the ability of AC2993 to improve beta cell function; and 3) the effects of immunosuppression on beta cell function.
Type I diabetes is an autoimmune disease, in which the immune system attacks the beta cells of the pancreas. These cells produce insulin, which regulates blood sugar. AC2993 may improve the pancreas's ability to produce insulin and help control blood sugar, but it may also activate the original immune response that caused the diabetes. Thus, this study will examine the effects of AC2993 alone as well as in combination with immunosuppressive drugs.
Read more
Patients between 18 and 60 years of age who have type I diabetes mellitus may be eligible for this 20-month study. They must have had diabetes for at least 5 years and require insulin treatment. Candidates will be screened with a questionnaire, followed by medical history and physical examination, blood and urine tests, a chest x-ray and skin test for tuberculosis, electrocardiogram (EKG), and arginine stimulated C-peptide test (see description below). Participants will undergo the following tests and procedures:
Advanced screening phase: Participants undergo a diabetes education program, including instruction on frequent blood glucose monitoring, dietary education on counting carbohydrates, intensive insulin therapy, review of signs and symptoms of low blood sugar (hypoglycemia), and potential treatment with glucagon shots.
Patients must administer insulin via an insulin pump or take at least four injections per day including glargine (Lantus) insulin.
4-month run-in phase
- Arginine-stimulated C-peptide test: This test measures the body's insulin production. The patient is injected with a liquid containing arginine, a normal constituent of food that increases insulin release from beta cells into the blood stream. After the injection, seven blood samples are collected over 10 minutes.
- Mixed meal stimulated C-peptide test with acetaminophen: This test assesses the response of the beta cells to an ordinary meal and the time it takes for food to pass through the stomach. The patient drinks a food supplement and takes acetaminophen (Tylenol). Blood samples are then drawn through a catheter (plastic tube placed in a vein) every 30 minutes for 4 hours to measure levels of various hormones and the concentration of acetaminophen.
- Euglycemic clamp: This test measures the body's level of insulin resistance by measuring the amount of glucose necessary to compensate for an increased insulin level while maintaining a prespecified blood glucose level.
Read the detailed description
Type I diabetes mellitus (T1DM) typically results from immune mediated destruction of pancreatic beta cells. Previous studies indicate that some patients retain the capacity for limited endogenous insulin production. AC2993 (synthetic exendin-4) has been shown in preclinical and in human studies to have several potentially beneficial antidiabetic actions, including recovery and neogenesis of pancreatic islets. Thus, we plan to enroll adults with long-standing T1DM who have some C-peptide secretion indicating residual beta cell mass. The latter will be targeted by AC2993. Due to the possibility of stimulating the underlying autoimmune process of T1DM, especially if islet regeneration occurs, we will subject half of the enrollees to immunosuppression. We plan to study the effects of AC2993 alone, immunosuppression (daclizumab) alone, as well as the combination of AC2993 and immunosuppression on insulin secretion and glycemia control.
- Conditions
- Diabetes Mellitus
- Being tested
- AC2993 (exenatide), daclizumab (immunosuppressive)
- Keywords
- Type 1 Diabetes Mellitus (T1DM), Beta-Cell, C-Peptide, Immunosuppression, Insulin, Islet, Function, AC2993 (Synthetic Exendin-4), Diabetes Mellitus, Type I Diabetes Mellitus, T1DM
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AC2993 (exenatide)Drug
Dose-escalation beginning with 2.5 μg administered subcutaneously twice per day (BID); then to 2.5 μg four times a day (QID); then to 5 μg four times a day; then to 10 μg four times a day.
daclizumab (immunosuppressive)Drug
2 mg/kg intravenously infused over 30 minutes every month for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Group 1 will receive immunosuppression and AC2993; then immunosuppression only Receives: Drug: AC2993 (exenatide); Drug: daclizumab (immunosuppressive) |
| Group 2 | Experimental | Group 2 will receive AC2993 only; then neither immunosuppression nor AC2993 Receives: Drug: AC2993 (exenatide); Drug: daclizumab (immunosuppressive) |
| Group 3 | Experimental | Group 3 will receive immunosuppression and AC2993; then immunosuppression and AC2993 Receives: Drug: AC2993 (exenatide); Drug: daclizumab (immunosuppressive) |
| Group 4 | Experimental | Group 4 will receive AC2993 only; then AC2993 only Receives: Drug: AC2993 (exenatide); Drug: daclizumab (immunosuppressive) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in basal C-peptide level
Assess whether patients treated with AC2993 (with or without concomitant immunosuppression) will display at least a 50% improvement in their basal C-peptide level. C-peptide level is a surrogate measure for insulin production.
Measured: baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2003 (estimated)
- Study startJul 2003
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vice President, Research and Development, MD, Study director, Amylin Pharmaceuticals, LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00064714
- Sponsor's protocol ID
- 030245 (2993T1-101)
- Other IDs
- 03-DK-0245
- Status last verified
- Jan 2015
- First submitted
- 10 Jul 2003
- Last updated
- 11 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Bach JF, Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu Rev Immunol. 2001;19:131-61. doi: 10.1146/annurev.immunol.19.1.131.
PubMed 11244033Lernmark A, Barmeier H, Dube S, Hagopian W, Karlsen A, Wassmuth R. Autoimmunity of diabetes. Endocrinol Metab Clin North Am. 1991 Sep;20(3):589-617.
PubMed 1935920Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature. 2001 Dec 13;414(6865):792-8. doi: 10.1038/414792a.
PubMed 11742411Rother KI, Spain LM, Wesley RA, Digon BJ 3rd, Baron A, Chen K, Nelson P, Dosch HM, Palmer JP, Brooks-Worrell B, Ring M, Harlan DM. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care. 2009 Dec;32(12):2251-7. doi: 10.2337/dc09-0773. Epub 2009 Oct 6.
PubMed 19808924
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of AC 2993 (Synthetic Exendin-4) - Administered Alone or in Combination With Daclizumab - on Islet Function in Patients With Type I Diabetes
- ClinicalTrials.gov ID
- NCT00064714
- Acronym / sponsor ID
- 030245 (2993T1-101)
- Conditions
- Diabetes Mellitus
- Keywords
- Type 1 Diabetes Mellitus (T1DM), Beta-Cell, C-Peptide, Immunosuppression, Insulin, Islet, Function, AC2993 (Synthetic Exendin-4)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2003
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 11 Jul 2003 (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.
This study will determine 1) the safety of AC2993 in patients with type I diabetes; 2) the ability of AC2993 to improve beta cell function; and 3) the effects of immunosuppression on beta cell function.
Type I diabetes is an autoimmune disease, in which the immune system attacks the beta cells of the pancreas. These cells produce insulin, which regulates blood sugar. AC2993 may improve the pancreas's ability to produce insulin and help control blood sugar, but it may also activate the original immune response that caused the diabetes. Thus, this study will examine the effects of AC2993 alone as well as in combination with immunosuppressive drugs.
Patients between 18 and 60 years of age who have type I diabetes mellitus may be eligible for this 20-month study. They must have had diabetes for at least 5 years and require insulin treatment. Candidates will be screened with a questionnaire, followed by medical history and physical examination, blood and urine tests, a chest x-ray and skin test for tuberculosis, electrocardiogram (EKG), and arginine stimulated C-peptide test (see description below). Participants will undergo the following tests and procedures:
Advanced screening phase: Participants undergo a diabetes education program, including instruction on frequent blood glucose monitoring, dietary education on counting carbohydrates, intensive insulin therapy, review of signs and symptoms of low blood sugar (hypoglycemia), and potential treatment with glucagon shots.
Patients must administer insulin via an insulin pump or take at least four injections per day including glargine (Lantus) insulin.
4-month run-in phase
- Arginine-stimulated C-peptide test: This test measures the body's insulin production. The patient is injected with a liquid containing arginine, a normal constituent of food that increases insulin release from beta cells into the blood stream. After the injection, seven blood samples are collected over 10 minutes.
- Mixed meal stimulated C-peptide test with acetaminophen: This test assesses the response of the beta cells to an ordinary meal and the time it takes for food to pass through the stomach. The patient drinks a food supplement and takes acetaminophen (Tylenol). Blood samples are then drawn through a catheter (plastic tube placed in a vein) every 30 minutes for 4 hours to measure levels of various hormones and the concentration of acetaminophen.
- Euglycemic clamp: This test measures the body's level of insulin resistance by measuring the amount of glucose necessary to compensate for an increased insulin level while maintaining a prespecified blood glucose level.
Detailed description
Type I diabetes mellitus (T1DM) typically results from immune mediated destruction of pancreatic beta cells. Previous studies indicate that some patients retain the capacity for limited endogenous insulin production. AC2993 (synthetic exendin-4) has been shown in preclinical and in human studies to have several potentially beneficial antidiabetic actions, including recovery and neogenesis of pancreatic islets. Thus, we plan to enroll adults with long-standing T1DM who have some C-peptide secretion indicating residual beta cell mass. The latter will be targeted by AC2993. Due to the possibility of stimulating the underlying autoimmune process of T1DM, especially if islet regeneration occurs, we will subject half of the enrollees to immunosuppression. We plan to study the effects of AC2993 alone, immunosuppression (daclizumab) alone, as well as the combination of AC2993 and immunosuppression on insulin secretion and glycemia control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: AC2993 (exenatide), Drug: daclizumab (immunosuppressive)Group 1 will receive immunosuppression and AC2993; then immunosuppression only |
| Group 2 | Experimental | Drug: AC2993 (exenatide), Drug: daclizumab (immunosuppressive)Group 2 will receive AC2993 only; then neither immunosuppression nor AC2993 |
| Group 3 | Experimental | Drug: AC2993 (exenatide), Drug: daclizumab (immunosuppressive)Group 3 will receive immunosuppression and AC2993; then immunosuppression and AC2993 |
| Group 4 | Experimental | Drug: AC2993 (exenatide), Drug: daclizumab (immunosuppressive)Group 4 will receive AC2993 only; then AC2993 only |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Insulin dependence (with an insulin requirement less than 0.8 units/kg/day).
- Current or past anti-islet antibodies (anti-insulin before initiation of insulin therapy, anti-islet cell (ICA), anti-tyrosine phosphatase IA-2, and/or anti-glutamic acid decarboxylase (GAD65) antibodies).
- BMI greater than or equal to 20 kg/m(2) and less than or equal to 30 kg/m(2).
- C-peptide greater than or equal to 0.3 and less than or equal to 1.2 ng/mL at baseline or during an arginine-stimulated C-peptide test.
- Age 18 to 60 years, inclusive.
Key exclusion criteria (14 listed)
- Symptomatic gastroparesis.
- Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24-hour urine albumin greater than 300 mg.
- Insulin requirements greater than 0.8 units/kg/day.
- Hypoglycemia unawareness: Unless easily corrected via simple modifications in the patient's diabetes regimen, the potential enrollee will be excluded if he/she has suffered greater than or equal to 2 episodes of severe hypoglycemia during the most recent 12 months, defined as requiring assistance from a third party, receiving assistance from medics, visiting an ER or being hospitalized due to the hypoglycemia.
- Evidence of chronic infection.
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 |
|---|---|---|
| AC2993 (exenatide)Dose-escalation beginning with 2.5 μg administered subcutaneously twice per day (BID); then to 2.5 μg four times a day (QID); then to 5 μg four times a day; then to 10 μg four times a day. | Drug | Group 1, Group 2, Group 3, Group 4 |
| daclizumab (immunosuppressive)2 mg/kg intravenously infused over 30 minutes every month for 12 months | Drug | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
Change in basal C-peptide level
Time frame: baseline and 6 months
Assess whether patients treated with AC2993 (with or without concomitant immunosuppression) will display at least a 50% improvement in their basal C-peptide level. C-peptide level is a surrogate measure for insulin production.
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 11 Mar 2015.
- Background: PubMed 11244033Bach JF, Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu Rev Immunol. 2001;19:131-61. doi: 10.1146/annurev.immunol.19.1.131.
- Background: PubMed 1935920Lernmark A, Barmeier H, Dube S, Hagopian W, Karlsen A, Wassmuth R. Autoimmunity of diabetes. Endocrinol Metab Clin North Am. 1991 Sep;20(3):589-617.
- Background: PubMed 11742411Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature. 2001 Dec 13;414(6865):792-8. doi: 10.1038/414792a.
- Derived from this study: PubMed 19808924Rother KI, Spain LM, Wesley RA, Digon BJ 3rd, Baron A, Chen K, Nelson P, Dosch HM, Palmer JP, Brooks-Worrell B, Ring M, Harlan DM. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care. 2009 Dec;32(12):2251-7. doi: 10.2337/dc09-0773. Epub 2009 Oct 6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Vice President, Research and Development, MD study director
Amylin Pharmaceuticals, LLC.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AC2993 (exenatide) and daclizumab (immunosuppressive) in people with Diabetes Mellitus, run by AstraZeneca 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 6 inclusion and 14 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 11 Mar 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 basal C-peptide level (time frame: baseline and 6 months). 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 NCT00064714, which also lists 4 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 11 Mar 2015.