Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
Information source: Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 1 Diabetes
Intervention: Pramlintide (Drug); Exenatide (Drug); Insulin (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Albert Einstein College of Medicine of Yeshiva University Official(s) and/or principal investigator(s): Rubina A Heptulla, MD, Principal Investigator, Affiliation: Albert Einstein College of Medicine of Yeshiva University
Summary
The main purpose of the study is to determine the effects of 16 weeks of adjunctive
pramlintide or exenatide use on glycemic control in Type 1 Diabetes.
Clinical Details
Official title: Exenatide (Byetta) Vs Pramlintide (Symlin): Role in Post-prandial Hyperglycemia
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determine the effects of 16 weeks of adjunctive pramlintide or exenatide use on glycemic control in Type 1 diabetes mellitus.
Detailed description:
After signing an informed consent, prior to study enrollment, a screening evaluation will be
performed in the Clinical Research Center (CRC).
The evaluation will consist of: a medical history, a physical examination with vital signs,
Tanner staging, and a waist circumference. The following clinical laboratory tests will be
done: CBC, HbA1c, creatinine,Liver function tests, amylase,adiponectin, leptin, C-reactive
protein, lipid profile, IL-6, lipase, urine for pregnancy test (when appropriate) and
microalbumin. A urine pregnancy test will be done at each study visit in menstruating
females. Also an anti-GAD, ICA512, and anti-insulin antibody if they were not previously
done or if records are not available. Each subject will have a continuous glucose monitoring
sensor (CGMS) inserted and will need to wear it for 3 days (72 hours). A person,trained to
insert the subcutaneous sensor, will insert the sensor. The sensor is inserted
subcutaneously with an injector device. This site insertion is very similar to an insulin
pump site insertion. A recorder is attached to the sensor and records blood glucose data for
72 hours. The subject will need to test their blood glucose at least 4 times a day while
wearing the sensor. The subject will be asked to keep a log on diet, insulin and exercise
while wearing the CGMS. At the end of the 3 day sensing period, the subject will remove the
sensor and place the recorder on a charger. The sensor will be brought back by the subject
to Visit #1. A Mixed Meal Tolerance Test will be performed at this visit (as described
below): Preparation for Mixed Meal Tolerance Test (MMTT)
1. The test will be performed in the morning (between 7 and 10 AM)
2. Test will be conducted only if fasting value by capillary blood glucose meter is
between 70-200 mg/dl (3. 9-11. 1 mMol). If the blood glucose prior to start of MMTT is
greater than 350 mg/dl, then urine ketones will be measured. If a subject's blood
glucose is less than 70 mg/dl before the Mixed Meal Tolerance Test, they will receive
5-10 grams of dextrose 50% by IV. If a subject develops hyperglycemia after the MMTT
(which is expected), they will receive a supplemental bolus of fast acting insulin
based on their usual insulin sensitivity factor. The subject will be instructed by the
study staff on the amount needed. The subject will administer the bolus themselves
3. Participants on injections will not withhold taking long acting insulin on the morning
of the test. Participants can take very short acting insulin (e. g. Humalog or Novolog)
up to 2 hours before the test if necessary and then that will be withheld during the
test.
4. Participants on insulin pumps will continue with the normal basal rate. Participants
can take very short acting insulin (e. g. Humalog or NovoLog) up to 2 hours before the
test if necessary.
5. The participant will be fasting for at least 8 hours and have had no food or drink
(with the exception of water).
6. Local anesthetics may be used as needed to start the I. V. line. Conducting the Mixed
Meal Tolerance Test (MMTT)
1. Baseline blood samples will be drawn at - 30 minutes; -10 minutes and 0 minutes
(immediately before the participant starts drinking the liquid meal) Baseline samples will
include glucose, insulin, C-peptide, amylin, GLP-1, glucagon and active ghrelin. 2. The
participant will have a standardized liquid meal: Boost HP 6 ml/kg, with a maximum of 360
ml, to be ingested within 5 minutes. 3. Blood samples will be drawn at times: 15, 30, 60, 90
and 120 minutes for glucose, insulin, C-peptide, amylin, GLP-1, active ghrelin and glucagon
after the start of ingestion of Boost. 4. After the test is completed, the participant will
receive their usual morning dose of short acting insulin analog. The short acting analog
will be dosed according to the subject's usual sensitivity factor and insulin to
carbohydrate ratio for breakfast as prescribed by the investigator. Subjects on insulin pump
therapy will receive a short acting analog via the pump dosed according to the subject's
usual sensitivity factor and insulin to carbohydrate ratio for breakfast as prescribed by
the investigator. Subjects will receive a meal tray once the premeal insulin is
administered.
A total of 107. 6 ml of blood will be drawn at the screening visit.
Visit 1 (0 months):
If subjects qualify after screening, they will have the opportunity to enroll in the study.
They will meet with a study coordinator in the CRC to make adjustments to their insulin
dosage (if necessary) to optimize treatment and improve glycemic control. As shown in the
preliminary data section, insulin glargine (Lantus), a long acting analog, may be used when
mixed with short acting insulin analogs so as to decrease the total number of injections.
This may also increase compliance to the medication regimen. Parental supervision for
medication administration will be advised. Hypoglycemic events and adherence to insulin
regimen will be noted. QOL questionnaires will be administered. Subjects will have vital
signs, waist circumference, HbA1C, Glycomark, and a urine pregnancy test (as
appropriate).Dual-emission X-ray absorptiometry (DEXA) body scan will be done on this day to
estimate total body fat. Patients will also be asked to bring in food diary kept for 3 days
so that it can be analyzed for calories being consumed. During the entire study period,
subjects will be assessed using a home blood glucose monitor that will electronically
transfer data to PI (Glucomon). Data will be reviewed daily for weeks 1 and 2, and then once
a week for weeks 3 and 4. Starting at week 5, data will be reviewed once every two weeks for
the remainder of the study. Contact will be similar for all subjects. Subjects will receive
their Glucomon at this visit. At this visit, subjects will be randomized into one of three
possible groups.
Randomization: Subjects will be randomized using a random number table. Group 1: Pramlintide
+ Insulin Group 2: Exenatide + Insulin Group 3: Insulin monotherapy
Study Medications:
Exenatide dosing: Exenatide will be started at 1. 25 mcg as previously determined by us in an
earlier study. Exenatide injection will be given subcutaneously twice a day (within 30
minutes after the start of the meal) and will be separate from insulin injections. Exenatide
dose will be titrated to 2. 5 or 5 mcg (depending on response) to keep 2 hr post-prandial
blood glucose concentrations below 200 mg/dl. Initially, premeal bolus insulin dose will be
reduced by 30%. Basal insulin dose will not be changed. Insulin dose may be increased if
pre-meal blood glucose concentrations are greater than 150 mg/dl or to decrease
post-prandial hyperglycemia.
Pramlintide dosing: Based on our preliminary studies, pramlintide will be started at 15 mcg
and then titrated up to 30-45 mcg and capped at 60 mcg. This will be based on demonstration
of acceptable post-prandial glucose excursions without hypoglycemia. Subjects will receive
pramlintide subcutaneously twice a day (within 30 minutes after the start of the meal) and
will be separate from insulin injections. Initially, premeal bolus insulin dose will be
reduced by 30%.Insulin dose may be increased if pre-meal blood glucose concentrations are
greater than 150 mg/dl or to decrease post-prandial hyperglycemia.
At the outset, we will decrease premeal bolus insulin dose by 30% for both groups, but
insulin may be increased as necessary once the subjects are better able to tolerate the
drugs (personal communications regarding unpublished data with Dr. David Maggs, Amylin
pharmaceuticals, on the management of exenatide and/or pramlintide with insulin).
Insulin monotherapy: Subjects randomized to insulin monotherapy will continue on either
long-acting and short acting insulin analogs or subcutaneous insulin pump therapy. Insulin
dose changes will only be made to optimize therapy.
A total of 5. 5 ml of blood will be drawn at the Visit 1.
Visit 2 (1 month):
Subjects will have vital signs, waist circumference, HbA1C, Glycomark, and a urine pregnancy
test (as appropriate).
Adherence to insulin/medication regimen and adverse event reporting will be obtained.
A total of 5. 5 ml of blood will be drawn at the Visit 2.
Visit 3 (4 months):
Subjects will undergo a medical history, physical examination, vital signs, waist
circumference, HbA1C, Glycomark,amylase, lipase, Liver function tests, CBC, creatinine,
adiponectin, leptin, C-reactive protein, lipid profile, IL-6, and a urine pregnancy test (as
appropriate) . Adherence to insulin/medication regimen and adverse event reporting will be
obtained. Quality of Life (QOL) questionnaires will be repeated. Additionally, subjects will
come in fasting and undergo a MMTT as described in the Screening visit but if subjects are
on pramlintide/ exenatide (Byetta) they will receive that dose prior to the boost
administration. DEXA scan will be done on this day to estimate total body fat. Patients will
also be asked to bring in food diary kept for 3 days so that it can be analyzed for calories
being consumed. Each subject with have a continuous glucose monitoring sensor (CGMS)
inserted and will need to wear it for 3 days (72 hours). A person, trained to insert the
subcutaneous sensor, will insert the sensor. The subject will receive instruction on
completion of logsheets and how to properly remove the sensor. Pramlintide and exenatide
will be stopped after the subject removes the sensor which is again 3 days from its
insertion. Each family would be given a prepaid envelope to mail back the sensor recorder
and the remaining study medication. A total of 104. 6 ml of blood will be drawn at the Visit
3. Control subjects during the MMTT will receive pramlintide or exenatide as a one time dose
without insulin.
Visit 4 (6-7 months):
This will be a post-study visit. Subjects will undergo a medical history, physical
examination, vital signs, waist circumference. This visit will be similar to visit 3 for
testing and lab work and pregnancy test (as appropriate). Except that the subject will not
have DEXA scan and a Continuos Glucose Monitoring Sensor. If the subject received
pramlintide previously as study drug in visit 3 they will receive exenatide as a one time
dose with the MMTT. QOL questionnaires will be repeated. Adherence to insulin regimen and
adverse event reporting will be obtained. Subjects will return their Glucomon and all the
blood glucose log books at this visit. A total of 104. 6 ml of blood will be drawn at the
Visit 4.
During the entire study period, subjects will be assessed using data collected from a study
issued home blood glucose monitor. The subject's blood glucose data will be electronically
transmitted to the PI ensuring data security and patient privacy. Data will be reviewed
daily for weeks 1 and 2, and then once a week for weeks 3 and 4. Starting at week 5,data
will be reviewed once every two weeks for the remainder of the study.
Eligibility
Minimum age: 12 Years.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Age of 12 to 21 years.
2. HbA1C less than 9%
3. Subjects must be on intensive insulin management
4. Tanner stage greater than or equal to 3
5. Having Type 1 Diabetes for at least one year
6. Type 1Diabetes defined by ADA criteria and having at least one of the following
antibodies a. Anti-GAD (glutamic acid decarboxylase) b. Anti-islet cell 512 (ICA512)
c. Anti-insulin
7. Willing to give consent.
Exclusion Criteria:
1. Type 2 diabetes.
2. Having any other chronic condition except hypothyroidism stable on medications.
3. On chronic medications that may affect glucose excursions.
4. Anemia as defined as Hb less than 9 gm/dl.
5. Abnormal amylase, lipase or creatinine (twice normal).
6. Abnormal Liver function tests(three times above normal)
7. Unsupportive family environment as determined by clinicians and/or social workers.
8. Pregnant or lactating mothers
Locations and Contacts
Albert Einstein College of Medicine West Campus Clinical Research Center, Bronx, New York 10467, United States
Additional Information
Starting date: December 2010
Last updated: June 22, 2015
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