Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery

NCT01841359 | Completed Phase 4 Results

• 1 other identifier: Joslin 08-34
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether pramlintide (Symlin) will help to reduce the frequency and severity of hypoglycemia in individuals who have had gastric bypass surgery.

Conditions

Hypoglycemia; Evidence of Previous Gastric Surgery

Keywords

Hypoglycemia; Gastric bypass surgery

Outcome Measures

Primary Outcomes (1)

• Plasma Glucose Levels in Response to Mixed Meal Testing - Area Under the Curve for Plasma Glucose

  Baseline and post-treatment with pramlintide mixed meal testing plasma glucose values, area under the curve (AUC), calculated with the trapezoidal method. Plasma glucose was measured at timepoints (minutes): -5 (baseline), 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes.

  Levels assessed on the two days of mixed meal testing: the first occurring at baseline; and the second following 8 weeks of treatment with pramlintide.

Secondary Outcomes (10)

• Continuous Glucose Monitoring Maximum Sensor Glucose Values Prior to (Baseline) and During Pramlintide Therapy.

  During 8 week period of participation, V1-V2 (baseline CGM data over 3 days); V3-V4 (CGM data during treatment with three times per day (TID) pramlintide over 3 days)

• Continuous Glucose Monitoring Minimum Sensor Glucose Prior to (Baseline) and During Pramlintide Therapy.

  During 8 week period of participation, V1-V2 (baseline CGM data over 3 days); V3-V4 (CGM data during treatment with TID pramlintide over 3 days)

• Hypoglycemia - Percentage of Time Sensor Glucose Levels < 70 mg/dL Prior to (Baseline) and During Pramlintide Therapy.

  During 8 week period of participation, V1-V2 (baseline CGM data over 3 days); V3-V4 (CGM data during treatment with TID pramlintide over 3 days)

• Plasma Insulin Levels in Response to Mixed Meal Testing - Area Under the Curve for Plasma Insulin

  Levels assessed on the two days of mixed meal testing: the first occurring at baseline; and the second following 8 weeks of treatment with pramlintide.

• Satiety Score During Mixed Meal Testing at 120 Minutes

  Levels assessed on the two days of mixed meal testing at the 120 min time point: the first occurring at baseline (prior to treatment with pramlintide), and the second following 8 weeks of treatment with pramlintide.

Study Arms (2)

Baseline

NO INTERVENTION

Baseline Arm/Phase 1, is comprised of study visits 1 and 2. Visit 1: Screening visit. Eligible individuals who provided informed consent were asked to keep a 3-day log of food intake, blood glucose (8 per day), as well as any hypoglycemic symptoms, concurrent with a 3 day period of blinded (masked) continuous glucose monitoring device wear. Visit 2: a baseline mixed meal tolerance test was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom logs were reviewed.

Pramlintide

EXPERIMENTAL

At the end of Visit 2 (following the baseline mixed meal tolerance test), pramlintide was prescribed, with instructions for titration from minimal to maximal dose (15 to 120 µg). During the treatment phase (8 weeks), the participants were asked to keep record of all hypoglycemic symptoms and blood glucose measurements.. Visit 3: (week 4 of treatment) focused on evaluation of symptoms and side effects. Participants again completed a food and glucose diary for 3 days with concurrent wear of a blinded (masked) continuous glucose monitoring device. Visit 4: (week 8 of treatment), participants received a dose of pramlintide 15 minutes prior to undergoing a repeat mixed meal tolerance test. (the dose administered was the maximally tolerated dose of pramlintide used during the 8 week outpatient treatment phase).

Drug: Pramlintide

Interventions

Pramlintide DRUG

See description above (arm description).

Also known as: Symlin

Pramlintide

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• severe hypoglycemic episodes post-gastric bypass surgery
• normal fasting glucose
• age 21 to 65
• hypoglycemia must not have responded to dietary intervention (low glycemic index, controlled carbohydrate portions) and a trial of acarbose therapy at the maximally tolerated dose

You may not qualify if:

• Hypoglycemia in the fasting state (greater than 12 hours fast)
• History of preoperative diabetes mellitus
• Use of medications that affect gastrointestinal motility (e.g., cisapride, metoclopramide)
• Impaired renal function (creatinine clearance \< 20 ml/min or on dialysis
• Hepatic disease (defined as liver enzymes \> 2 times upper normal limit for alanine transaminase (ALT) and aspartate aminotransferase (AST))
• Blood donation for 2 months prior to the study.
• Severe hypoglycemic unawareness, as defined by inability to recognize adrenergic or neuroglycopenic symptoms of hypoglycemia despite detailed education

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (5)

• Patti ME, Goldfine AB. Hypoglycaemia following gastric bypass surgery--diabetes remission in the extreme? Diabetologia. 2010 Nov;53(11):2276-9. doi: 10.1007/s00125-010-1884-8. Epub 2010 Aug 21.

  PMID: 20730413 BACKGROUND

• Goldfine AB, Mun EC, Devine E, Bernier R, Baz-Hecht M, Jones DB, Schneider BE, Holst JJ, Patti ME. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab. 2007 Dec;92(12):4678-85. doi: 10.1210/jc.2007-0918. Epub 2007 Sep 25.

  PMID: 17895322 BACKGROUND

• Patti ME, McMahon G, Mun EC, Bitton A, Holst JJ, Goldsmith J, Hanto DW, Callery M, Arky R, Nose V, Bonner-Weir S, Goldfine AB. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia. 2005 Nov;48(11):2236-40. doi: 10.1007/s00125-005-1933-x. Epub 2005 Sep 30.

  PMID: 16195867 BACKGROUND

• Goldfine AB, Mun E, Patti ME. Hyperinsulinemic hypoglycemia following gastric bypass surgery for obesity. Current Opinion in Endocrinology and Diabetes 13: 419-24, 2006.

  BACKGROUND

• Sheehan A, Goldfine A, Bajwa M, Wolfs D, Kozuka C, Piper J, Fowler K, Patti ME. Pramlintide for post-bariatric hypoglycaemia. Diabetes Obes Metab. 2022 Jun;24(6):1021-1028. doi: 10.1111/dom.14665. Epub 2022 Mar 9.

  PMID: 35137513 BACKGROUND

MeSH Terms

Conditions

Hypoglycemia

Interventions

pramlintide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Mary Elizabeth Patti, MD
• Organization: Joslin Diabetes Center

MaryElizabeth.Patti@joslin.harvard.edu

6173092635

Study Officials

• Mary E. Patti, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants in this study were asked to complete 4 study visits. Arm/Phase 1: Baseline: Study V1 was a screening visit. Participants kept a 3-day log of food intake, blood glucose (8 per day), as well as any hypoglycemic symptoms. At V2, a baseline mixed meal tolerance test (MMTT) was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom logs were reviewed. Arm / Phase 2: Pramlintide treatment Pramlintide was prescribed at the end of visit 2 (following MMTT), with instructions for titration from minimal to maximal dose (15 to 120 µg). During treatment, the participants kept a record of all hypoglycemic symptoms and blood glucose measurements at those times. Study visit 3 occurred at week 4 of treatment and focused on evaluation of symptoms and side effects. Participants again completed a food and glucose diary for 3 days. During study visit 4 (week 8 of treatment), participants underwent a repeat MMTT.

Study Record Dates

• First Submitted: April 24, 2013
• First Posted: April 26, 2013
• Study Start: February 2, 2010
• Primary Completion: July 1, 2016
• Study Completion: February 8, 2022
• Last Updated: June 29, 2023
• Results First Posted: May 26, 2022

Record last verified: 2023-06

Locations

US (1)