Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
Condition: Hypoglycemia; Evidence of Previous Gastric Surgery
MeSH terms: Hypoglycemia
Study type: Interventional
Phase: Phase 4

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.
    

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. Concurrently participants will wear a
      professional (blinded) continuous glucose monitoring (CGM) device for 3 days. 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, while also
      wearing a professional (blinded) CGM. 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, receiving a dose of pramlintide prior to the start of the mixed meal, for
      comparison with the pre-treatment (baseline) results.
    

Intervention name(s): Pramlintide
Intervention type(s): Drug
Intervention description(s): See description above (arm description).
Other intervention name(s): Symlin
Intervention MeSH terms: Pramlintide
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hypoglycemia; Gastric bypass surgery