Efficacy Study of High Dose Symlin to Treat Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The hypothesis of the study is that those obese patients with type 2 diabetes mellitus who do not respond to the FDA approved dose of 120 mcg of pramlintide (Symlin®) 3 times daily with expected glucose control require higher than FDA approved dosage. The primary objective of the study is to determine whether higher doses of pramlintide (Symlin®) in patients with type 2 diabetes mellitus control glucose better than the FDA approved dose of 120 mcg three times daily. The secondary objectives include proving whether higher dose pramlintide (Symlin®) is more efficacious in causing weight loss and reduction in waist circumference than standard dose pramlintide (Symlin®),to determine whether blood levels of certain hormones correlate with need for higher dose therapy,and to determine whether or not the rate of common adverse effects exceeds the maximum FDA approved pramlintide (Symlin®) dose of 120 mcg three times daily.

Official Title
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Symlin® Dose Escalation Efficacy vs. Conventional Therapy in Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Pramlintide
* Drug: Pramlintide
* Drug: Pramlintide
* Drug: Pramlintide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years. Type 2 diabetes mellitus. Obese (BMI > 30 kg/m2), waist circ. >35 women, >40 men. Basal insulin plus at least 2 injections of mealtime insulin daily or pre-mixed insulin. On stable insulin dose for at least 3 mos (baseline + 20%, no minimum). If pramlintide treated, on stable full dose for at least 3 months. A1c > 7.0% and < 9.0%. Women of childbearing age if using a reliable form of birth control. Women of childbearing age if post tubal ligation or surgical menopause. Able to consent. Willing to perform self-monitoring of glucose. Willing to attend study visits. Written informed consent to participate in the study. Agreement to maintain prior diet and exercise throughout the full course of the study. Exclusion Criteria: Age <18 or >80 years. Confirmed gastroparesis or taking medications affecting gastric motility. A1c <7.0% or >9.0%. Recurrent severe hypoglycemia or hypoglycemic unawareness. CHF. Creatinine clearance <30 ml/min. History of MI <6 mos prior to enrollment. History of ventricular arrhythmia. History of cancer or chemotherapy <6 mos prior to enrollment. Laboratory abnormalities as follows: Liver enzymes >3X ULN. Hematocrit less than 30. Serum creatinine >2.5 mg/dl. Fasting triglycerides >500 mg/dl. Cirrhosis. Pregnancy or nursing. Inability to provide consent. Unwilling to attend study visits. Unwilling to perform self-monitoring of glucose. Chronic oral or parenteral glucocorticoid therapy (over one week of treatment) within 3 months prior to screening. Investigational drug treatment within 3 months prior to screening. Donation of blood, significant blood loss or transfusion within 3 months of screening. History of acromegaly or Cushing's syndrome. Use of prohibited concomitant medications. Type 1 diabetes mellitus. Acute metabolic complication (hyperosmolar state) <6 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Symlin Naive, Usual Dose<br>Symlin 120 mcg three times daily in patients not previously treated with pramlintide before the study. | Drug: Pramlintide<br>* 120 mcg SQ three times daily for 6 months.<br>|
| Experimental: Symlin Naive, Dose Escalation<br>Escalation of pramlintide dose to 360 mcg three times daily in patients not taking pramlintide prior to study. | Drug: Pramlintide<br>* 360 mcg SQ three times daily for 6 months<br>|
| Active Comparator: Symlin treated, Usual Dose<br>pramlintide 120 mcg three times daily in patients who have been treated with pramlintide 120 mcg prior to the trial. | Drug: Pramlintide<br>* 120 mcg SQ three times daily for 6 months<br>|
| Experimental: Symlin Treated, Dose Escalation<br>pramlintide 360 mcg three times daily in patients previously treated with 120 mcg prior to the study. | Drug: Pramlintide<br>* 360 mcg SQ three times daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose control | A1c Fasting plasma glucose Post-prandial glucose Glycomark | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss | Weight, BMI, Waist circumference. | 6 months | 
| amylin level | does initial blood amylin level correlate with need for higher dose pramlintide? | initial | 
| glucagon level | Does change in glucagon level correlate with glycemic response. | 6 months | 
| adverse effects | Whether or not the rate of common adverse effects exceeds the maximum FDA approved pramlintide (Symlin®) dose of 120 mcg TID (as compared to the clinical practice study) - GI: nausea 30% and Hypoglycemia: medically assisted 0.7% or patient ascertained 0.7%. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pramlintide, glucose, type 2 diabetes mellitus, amylin