Trial Outcomes & Findings for Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery (NCT NCT01841359)
NCT ID: NCT01841359
Last Updated: 2023-06-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
22 participants
Primary outcome timeframe
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.
Results posted on
2023-06-29
Participant Flow
Participants with post-bariatric hypoglycemia (PBH) following gastric bypass were recruited from outpatient clinics at Joslin Diabetes Center, Boston, Massachusetts for an open label study of pramlintide efficacy over 8 weeks.
Participant milestones
| Measure |
Pramlintide (Symlin)
Participants in this study were asked to complete 4 study visits. Study visit 1 was a 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. At study visit 2, a baseline mixed meal tolerance test was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom log was reviewed. Pramlintide was prescribed, 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 occured 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 mixed meal tolerance test.
Pramlintide: See description above (arm description).
|
|---|---|
|
Overall Study
STARTED
|
22
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Pramlintide (Symlin)
Participants in this study were asked to complete 4 study visits. Study visit 1 was a 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. At study visit 2, a baseline mixed meal tolerance test was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom log was reviewed. Pramlintide was prescribed, 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 occured 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 mixed meal tolerance test.
Pramlintide: See description above (arm description).
|
|---|---|
|
Overall Study
Underwent reversal of Roux-en-Y gastric bypass (RYGB)
|
2
|
|
Overall Study
Concommitant medical issues
|
2
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Did not receive study drug at visit 4 prior to mixed meal testing
|
1
|
Baseline Characteristics
Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
Baseline characteristics by cohort
| Measure |
Pramlintide (Symlin)
n=14 Participants
Participants in this study completed 4 study visits. Study visit 1 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 study visit 2, a baseline mixed meal tolerance test were performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom log was reviewed. Pramlintide was prescribed, 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 mixed meal tolerance test.
Pramlintide: See description above (arm description).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
60.2 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
|
Pre-operative BMI
|
46.8 kg/m^2
STANDARD_DEVIATION 6.2 • n=5 Participants
|
|
Current BMI
|
29.6 kg/m^2
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Onset of hypoglycemia (years since) surgery
|
2.9 years
STANDARD_DEVIATION 2.9 • n=5 Participants
|
|
Time Since RYGB (years)
|
6.2 years
STANDARD_DEVIATION 2.7 • n=5 Participants
|
|
Preoperative history of diabetes mellitus (DM) or gestational DM
|
3 Participants
n=5 Participants
|
|
Family history of DM in first-degree relative
|
6 Participants
n=5 Participants
|
|
Possible hypoglycemia symptoms present preoperatively (self-report)
|
2 Participants
n=5 Participants
|
|
Hypoglycemia frequency (self-report) - Daily or more
|
1 Participants
n=5 Participants
|
|
Hypoglycemia frequency (self-report) - Weekly or more (but not daily)
|
7 Participants
n=5 Participants
|
|
Hypoglycemia frequency (self-report) - Monthly or more (but not weekly)
|
1 Participants
n=5 Participants
|
|
Systolic Blood Pressure Supine
|
119.1 mmHg
STANDARD_DEVIATION 12.5 • n=5 Participants
|
|
Diastolic Blood Pressure Supine
|
67.8 mmHg
STANDARD_DEVIATION 10.3 • n=5 Participants
|
|
Cholesterol (mg/dL)
|
169.6 mg/dL
STANDARD_DEVIATION 18.2 • n=5 Participants
|
|
Triglycerides (mg/dl)
|
75.2 mg/dL
STANDARD_DEVIATION 20.2 • n=5 Participants
|
|
HDL (mg/dl)
|
64.6 mg/dL
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Current therapy with acarbose
|
8 Participants
n=5 Participants
|
|
Current therapy with diazoxide
|
0 Participants
n=5 Participants
|
|
Current therapy with octreotide
|
1 Participants
n=5 Participants
|
|
Current therapy - medical nutrition therapy alone
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Analysis was for the 14 participants who completed all study visits.
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.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Plasma Glucose Levels in Response to Mixed Meal Testing - Area Under the Curve for Plasma Glucose
|
2828 mg*min/dL
Standard Deviation 3255
|
2893 mg*min/dL
Standard Deviation 2770
|
SECONDARY outcome
Timeframe: 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)Population: Analysis was for the participants with available CGM data who completed all study visits in this sequential design. Note that the number of participants analyzed for CGM related outcomes differs from the number of participants analyzed in the other outcomes due to incomplete CGM data.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=13 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=10 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Continuous Glucose Monitoring Maximum Sensor Glucose Values Prior to (Baseline) and During Pramlintide Therapy.
|
172 mg/dL
Standard Deviation 50.98
|
188 mg/dL
Standard Deviation 43.6
|
SECONDARY outcome
Timeframe: 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)Population: Analysis was for the participants with available CGM data who completed all study visits in this sequential design. Note that the number of participants analyzed for CGM related outcomes differs from the number of participants analyzed in the other outcomes due to incomplete CGM data.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=13 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=10 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Continuous Glucose Monitoring Minimum Sensor Glucose Prior to (Baseline) and During Pramlintide Therapy.
|
54 mg/dL
Standard Deviation 14.68
|
56.6 mg/dL
Standard Deviation 11.44
|
SECONDARY outcome
Timeframe: 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)Population: Analysis was for the participants with available CGM data who completed all study visits in this sequential design. Note that the number of participants analyzed for CGM related outcomes differs from the number of participants analyzed in the other outcomes due to incomplete CGM data.
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 time) assessed by continuous glucose monitoring.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=13 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=10 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Hypoglycemia - Percentage of Time Sensor Glucose Levels < 70 mg/dL Prior to (Baseline) and During Pramlintide Therapy.
|
8.85 percent time sensor glucose less than 70
Standard Deviation 9.23
|
5.60 percent time sensor glucose less than 70
Standard Deviation 5.32
|
SECONDARY outcome
Timeframe: 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.Pre- and post-treatment mixed meal testing plasma insulin levels area under the curve (AUC) was calculated with the trapezoidal method. Plasma insulin was measured at timepoints (minutes): -5 (baseline), 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Plasma Insulin Levels in Response to Mixed Meal Testing - Area Under the Curve for Plasma Insulin
|
3393 uIU*min/mL
Standard Deviation 2155
|
3501 uIU*min/mL
Standard Deviation 2683
|
SECONDARY outcome
Timeframe: 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.Satiety was analyzed using a visual analogue scale (1, very hungry to 10, not hungry), administered 120 minutes following ingestion of mixed meal.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Satiety Score During Mixed Meal Testing at 120 Minutes
|
4.57 satiety score
Standard Deviation 3.05
|
5.43 satiety score
Standard Deviation 2.51
|
SECONDARY outcome
Timeframe: 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.Dumping score was calculated using changes in pulse and hematocrit. Higher scores indicate more severe dumping. Scores ranged from -196 to 186.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Dumping Score During Mixed Meal Testing at Baseline and During Treatment With Pramlintide
|
28.89 dumping score
Standard Deviation 101.81
|
72.04 dumping score
Standard Deviation 70.93
|
SECONDARY outcome
Timeframe: 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)Population: Analysis was for the participants with available CGM data who completed all study visits in this sequential design. Note that the number of participants analyzed for CGM related outcomes differs from the number of participants analyzed in the other outcomes due to incomplete CGM data.
Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=13 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=10 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Number of Days With Minimum Sensor Glucose < 54 mg/dL as Measured by Continuous Glucose Monitoring.
|
1.31 days
Standard Deviation 1.49
|
0.56 days
Standard Deviation 0.73
|
SECONDARY outcome
Timeframe: 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.Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Nadir Plasma Glucose Levels During Mixed Meal Testing at Baseline and During Treatment With Pramlintide
|
67.18 mg/dL
Standard Deviation 17.14
|
69.9 mg/dL
Standard Deviation 14.8
|
SECONDARY outcome
Timeframe: Assessed on the two days of mixed meal testing: the first occurring at baseline; and the second following 8 weeks of treatment with pramlintide.Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Time to Nadir Plasma Glucose During Mixed Meal Testing at Baseline and During Treatment With Pramlintide
|
64.29 minutes
Standard Deviation 40.52
|
66.43 minutes
Standard Deviation 48.77
|
SECONDARY outcome
Timeframe: Assessed on the two days of mixed meal testing: the first occurring at baseline; and the second following 8 weeks of treatment with pramlintide.Outcome measures
| Measure |
Baseline (Prior to Pramlintide Treatment) Mixed Meal #1
n=14 Participants
Mixed meal #1 performed prior to initiation of pramlintide treatment.
|
Pramlintide - Mixed Meal #2
n=14 Participants
Mixed meal #2 performed after 1 dose of pramlintide given 15 minutes prior to the mixed meal, at maximum tolerated dose achieved during the outpatient stage.
|
|---|---|---|
|
Number of Participants Requiring Rescue Treatment for Severe Hypoglycemia During Mixed Meal Testing (Visit 2 Baseline vs. Visit 4 Post-pramlintide Dosing)
|
6 number of participants
|
4 number of participants
|
Adverse Events
Pramlintide (Symlin)
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pramlintide (Symlin)
n=22 participants at risk
Participants in this study were asked to complete 4 study visits. Study visit 1 was a 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. At study visit 2, a baseline mixed meal tolerance test was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom log was reviewed. Pramlintide was prescribed, 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 occured 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 mixed meal tolerance test.
Pramlintide: See description above (arm description).
|
|---|---|
|
General disorders
Dehydration (r/t diarrhea)
|
4.5%
1/22 • Number of events 1 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Gastrointestinal disorders
Diarrhea (assoc. with dehydration requiring hospitalization)
|
4.5%
1/22 • Number of events 1 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
Other adverse events
| Measure |
Pramlintide (Symlin)
n=22 participants at risk
Participants in this study were asked to complete 4 study visits. Study visit 1 was a 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. At study visit 2, a baseline mixed meal tolerance test was performed. Glucose, hormonal responses, and satiety were assessed. Glucose and symptom log was reviewed. Pramlintide was prescribed, 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 occured 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 mixed meal tolerance test.
Pramlintide: See description above (arm description).
|
|---|---|
|
Endocrine disorders
Hypoglycemia
|
18.2%
4/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Endocrine disorders
Hyperglycemia
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Hepatobiliary disorders
Elevated liver enzymes
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Nausea
|
13.6%
3/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Altered taste (during treatment with study drug)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Psychiatric disorders
Ethanol abuse / intoxication
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Trembling
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Gastrointestinal disorders
Diarrhea (with urgency and incontinence)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Psychiatric disorders
Auditory hallucinations
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Cold feeling behind eyes.
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Nightmares
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Psychiatric disorders
Increase in baseline anxiety.
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Renal and urinary disorders
Symptoms of a urinary tract infection (UTI) (CVA tenderness w/ dysuria)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Hepatobiliary disorders
Cholecystitis (prior to treatment with study drug)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus infection (Visit 4, following treatment with study drug)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
|
General disorders
Weight loss (during study drug treatment)
|
4.5%
1/22 • For each participant, adverse event data was collected during their 8 week period of participation. Overall, the participant data was collected from April 2014 through May 2016.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place