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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Pramlintide; Drug: Pramlintide; Drug: Pramlintide

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Denville, New Jersey, United States, 07834
      • North Jersey Endocrine Consultants
  • New York
    • Staten Island, New York, United States, 10301
      • University Physicians Group
  • Pennsylvania
    • Langhorne, Pennsylvania, United States, 19047
      • St. Mary Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-80 years.
2. Type 2 diabetes mellitus.
3. Obese (BMI > 30 kg/m2), waist circ. >35" women, >40" men.
4. Basal insulin plus at least 2 injections of mealtime insulin daily or pre-mixed insulin.
5. On stable insulin dose for at least 3 mos (baseline + 20%, no minimum).
6. If pramlintide treated, on stable full dose for at least 3 months.
7. A1c > 7.0% and < 9.0%.
8. Women of childbearing age if using a reliable form of birth control.
9. Women of childbearing age if post tubal ligation or surgical menopause.
10. Able to consent.
11. Willing to perform self-monitoring of glucose.
12. Willing to attend study visits.
13. Written informed consent to participate in the study.
14. Agreement to maintain prior diet and exercise throughout the full course of the study.

Exclusion Criteria:

1. Age <18 or >80 years.
2. Confirmed gastroparesis or taking medications affecting gastric motility.
3. A1c <7.0% or >9.0%.
4. Recurrent severe hypoglycemia or hypoglycemic unawareness.
5. CHF.
6. Creatinine clearance <30 ml/min.
7. History of MI <6 mos prior to enrollment.
8. History of ventricular arrhythmia.
9. History of cancer or chemotherapy <6 mos prior to enrollment.

10. Laboratory abnormalities as follows:

    1. Liver enzymes >3X ULN.
    2. Hematocrit less than 30.
    3. Serum creatinine >2.5 mg/dl.
    4. Fasting triglycerides >500 mg/dl.
11. Cirrhosis.
12. Pregnancy or nursing.
13. Inability to provide consent.
14. Unwilling to attend study visits.
15. Unwilling to perform self-monitoring of glucose.
16. Chronic oral or parenteral glucocorticoid therapy (over one week of treatment) within 3 months prior to screening.
17. Investigational drug treatment within 3 months prior to screening.
18. Donation of blood, significant blood loss or transfusion within 3 months of screening.
19. History of acromegaly or Cushing's syndrome.
20. Use of prohibited concomitant medications.
21. Type 1 diabetes mellitus.
22. Acute metabolic complication (hyperosmolar state) <6 months prior to screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cheryl Rosenfeld, DO
• Collaborators: Amylin Pharmaceuticals, LLC.
• Investigators: Principal Investigator: Cheryl Rosenfeld, DO, North Jersey Endocrine Consultants; Principal Investigator: Jeffrey Rothman, MD, University Physicians Group Research; Principal Investigator: Alan Schorr, DO, St. Mary Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Anticipated): January 1, 2012
• Study Completion (Anticipated): April 1, 2012

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 3, 2010
• First Posted (Estimate): June 4, 2010

Study Record Updates

• Last Update Posted (Estimate): October 14, 2011
• Last Update Submitted That Met QC Criteria: October 13, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: type 2 diabetes mellitus; glucose; pramlintide; amylin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Appetite Depressants; Anti-Obesity Agents; Amylin Receptor Agonists; Pramlintide; Islet Amyloid Polypeptide
• Other Study ID Numbers: DEFCon2