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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01841359
Recruitment Status : Unknown
Verified April 2017 by Joslin Diabetes Center.
Recruitment status was:  Active, not recruiting
First Posted : April 26, 2013
Last Update Posted : April 26, 2017
Bristol-Myers Squibb
Information provided by (Responsible Party):
Joslin Diabetes Center

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.

Condition or disease Intervention/treatment Phase
Hypoglycemia Evidence of Previous Gastric Surgery Drug: Pramlintide Phase 4

Detailed Description:

This study is an open-label short-term proof of concept study. The investigators will administer pramlintide to patients with severe post-prandial hypoglycemia following gastric bypass, in order to determine whether pramlintide is effective in reducing the frequency or severity of hypoglycemia. Pramlintide will be prescribed for 8 weeks. In order to assess the efficacy of pramlintide to prevent post-prandial hypoglycemia and hypoglycemic symptoms, the investigators will compare (a) blood glucose measurements and frequency of hypoglycemic symptoms, before and at the end of the drug intervention, using both capillary glucose monitoring and continuous glucose monitoring, and (b) glycemic, hormonal, and energetic responses to a three-hour mixed meal tolerance test.

The study will utilize an open label design to evaluate the efficacy of pramlintide in patients who have had gastric bypass and have severe postprandial hypoglycemia. The study will not be randomized or blinded. The investigators will recruit 26 participants from Joslin Diabetes Center.

Briefly, participants in this study will be asked to complete 4 study visits. The first visit will be for screening. They will then be asked to keep a 3-day log in which they record food intake (including estimated portion sizes), blood glucoses eight times daily, as well as any hypoglycemic symptoms, before they initiate treatment. At a second study visit, they will undergo a mixed meal tolerance test, which will serve as a baseline evaluation. Patterns of (a) glucose excursions (initial postprandial peak, subsequent postprandial fall and potential hypoglycemia), and (b) hormonal responses (insulin, C-peptide, glucagon, incretins) will be assessed. At the end of the mixed meal, satiety will be assessed using a visual analog scale. Baseline hypoglycemia frequency and severity will be assessed by reviewing patient glucose and hypoglycemia symptom log recorded prior to the visit.

At the completion of visit 2, pramlintide will be prescribed, with instructions for titration of the drug from minimal to maximal dose (see titration schedule below) to help reduce the incidence of side effects. During the treatment period, the participants will keep a record of all hypoglycemic symptoms and blood glucose measurements at those times.

There will be one follow-up visit (visit 3) in the middle of the treatment period for evaluation of symptoms and tolerance of medication. During the last (eighth) week of treatment, for comparison with pre-treatment glycemia, participants will again complete a food diary, and measure and record blood glucoses eight times daily for 3 days. During that final week of the study, participants will also come to a fourth study visit, during which they will undergo a repeat mixed meal tolerance test for comparison with the pre-treatment results.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
Study Start Date : June 2013
Actual Primary Completion Date : July 2016
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arm Intervention/treatment
Pramlintide (Symlin)

Participants in this study will be asked to complete 4 study visits. Study visit 1 will be for screening. Eligible individuals who provide informed consent will be asked to keep a 3-day log of food intake, blood glucose (8 per day), as well as any hypoglycemic symptoms. At study visit 2, a baseline mixed meal tolerance test will be performed. Glucose, hormonal responses, and satiety will be assessed. Glucose and symptom log will be reviewed. Pramlintide will be prescribed, with instructions for titration from minimal to maximal dose (15 to 120 µg). During treatment, the participants will keep a record of all hypoglycemic symptoms and blood glucose measurements at those times.

Study visit 3 will occur at week 4 of treatment and focus on evaluation of symptoms and side effects. Participants will again complete a food and glucose diary for 3 days. During study visit 4 (week 8 of treatment), participants will undergo a repeat mixed meal tolerance test.

Drug: Pramlintide
See description above (arm description).
Other Name: Symlin

Primary Outcome Measures :
  1. Hypoglycemia [ Time Frame: 8 weeks ]
    The primary study endpoint will be assessment of clinical response to pramlintide treatment, as indicated by paired comparison of the frequency of glucose values under 70 mg/dl (expressed as percentage of day, assessed by continuous glucose monitoring). Additional parameters assessed for clinical efficacy include other glucose parameters derived from both capillary glucose and symptom monitoring for 5 days 8 times daily (average blood glucose, minimum blood glucose, frequency of reported symptoms, and frequency of glucose values < 70 mg/dl) and continuous glucose monitoring (including minimum glucose, frequency of glucose values >140 mg/dl, and maximum glucose values) prior to and during pramlintide therapy.

Secondary Outcome Measures :
  1. meal hormonal responses [ Time Frame: 8 weeks ]
    The secondary study endpoints will be assessment of pramlintide effects on mixed meal hormonal responses, including glucagon, insulin, and incretins. Additional comparisons will include measures of satiety and fasting and diet-induced thermogenesis and respiratory quotient. Pre- and post-treatment fasting values and postprandial values (peak values, area under curve) will be compared using a two-sided comparison of paired means.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 ALT and 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01841359

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United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Joslin Diabetes Center
Bristol-Myers Squibb
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Principal Investigator: Mary E. Patti, MD Joslin Diabetes Center

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Responsible Party: Joslin Diabetes Center Identifier: NCT01841359     History of Changes
Other Study ID Numbers: Joslin 08-34
First Posted: April 26, 2013    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: April 2017
Keywords provided by Joslin Diabetes Center:
Gastric bypass surgery
Additional relevant MeSH terms:
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Glucose Metabolism Disorders
Metabolic Diseases
Islet Amyloid Polypeptide
Hypoglycemic Agents
Physiological Effects of Drugs
Appetite Depressants
Anti-Obesity Agents
Amylin Receptor Agonists
Molecular Mechanisms of Pharmacological Action