CREON for the Treatment of Post-RYGB Hypoglycemia

Study Overview
=================
Brief Summary
-----------------
Hypoglycemia is an increasingly recognized complication of Roux-en-Y gastric bypass (RYGB) that is poorly understood and difficult to treat. Investigators hypothesize that after RYGB some patients have incomplete carbohydrate absorption in the small intestine which leads to inconsistent glucose levels and hypoglycemia during oral consumption of a meal. Investigators further hypothesize that pancreatic enzyme supplementation with (Creon) during meals and snacks will improve carbohydrate absorption and lead to more stable glucose levels in patients with post-RYGB hypoglycemia.

Detailed Description
-----------------
Primary Objective: Evaluate the feasibility and safety of Creon in the treatment of post-RYGB hypoglycemia as add-on therapy to a diet higher in protein and lower in carbohydrate. Secondary Objective: Evaluate utility of continuous glucose monitoring (CGM) in monitoring hypoglycemia as an adjunct to standard venous blood testing using a glucometer in post-RYGB hypoglycemia.

Official Title
-----------------
A Proof-of-Concept Study Using Pancreatic Enzyme Replacement for the Treatment of Post-Roux-en-Y Gastric Bypass Hypoglycemia

Conditions
-----------------
Hypoglycemia

Intervention / Treatment
-----------------
* Drug: Creon
* Other: Diet
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females 18 years and older At least 6 months post-RYGB surgery Clinical history of post-surgical hypoglycemia evident by subjective symptoms (i.e. tachycardia, sweating, hunger, confusion) and glucose monitoring demonstrating a venous blood sugars < 70 mg/dL Women must be postmenopausal, surgically sterile, not heterosexually active or heterosexually active using highly effective method of birth control Women of childbearing potential must have negative pregnancy test Subjects must have signed an informed consent document indicating they understand the purpose of and procedures required for the study and be willing to participate in the study Willing and able to adhere to restrictions and follow instructions specific to this study Adequate compliance in performing self-monitoring blood glucose (SMBG) testing at least three or more times per week and taking assigned medication dose as instructed Exclusion Criteria: Current or past history of type 1 or type 2 diabetes Known hypersensitivity to Creon Known hypersensitivity to pork-derived products Liver function studies 2 times the upper limit of normal (ALT & AST) and/or a GFR < 90 History of fibrosing colonic strictures History of gastroparesis, dysphagia, chronic abdominal pain, gastric outlet obstruction, chronic pancreatitis History of stomach, small intestine or colon surgery other than Roux-en-Y gastric bypass An active cancer of any type requiring concurrent treatment History of gout or hyperuricemia Current anemia requiring iron replacement Any clinically significant condition that in the opinion of the investigator would make participation not in the best interest or safety of the subject or could prevent limit or confound the specific endpoints assessments Not participating in any other research study Known history of drug or alcohol abuse within 6 months of screening visit Pregnancy or lactation (breastfeeding) Informed consent withdrawal by subject

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DIET<br>A registered dietician (RD) will meet with and thoroughly review the patients diet. The patient will be counseled on a diet lower in refined carbohydrates and higher in protein. | Other: Diet<br>* A registered dietician will meet with the subject and take a thorough review of the patient's dietary history. The subject will then be counseled on a lower carbohydrate and higher protein diet. This diet will be continued for the entire 12 week of the study. The registered dietician will reinforce dietary recommendations by phone on week 2, 4 and 8, respectively.<br>|
| Active Comparator: Creon<br>Subjects will be provided Creon at a dose of 500 units/kg of lipase to be taken with meals and snacks to see if this decreases frequency and severity of hypoglycemia. | Drug: Creon<br>* Creon is a porcine derived pancreatic enzyme supplement that comes in in fixed dose combinations of lipase, protease, and amylase, respectively. Dosing is based on lipase per kilograms per meal (i.e. lipase units/kg/meal). Subjects will be started at a dose of 500 units of lipase/kg/meal and snacks at week 4 and continued until week 8. A follow-up visit at week 6 will assess patient for tolerance to Creon and need for dosage adjustment. Formulations come in different fixed dose combinations as follows: Creon: Lipase 3000 USP units, protease 9500 USP units, and amylase 15,000 USP units Creon: Lipase 6000 USP units, protease 19,000 USP units, and amylase 30,000 USP units Creon: Lipase 12,000 USP units, protease 38,000 USP units, and amylase 60,000 USP units Creon: Lipase 24,000 USP units, protease 76,000 USP units, and amylase 120,000 USP units Creon: Lipase 36,000 USP units, protease 114,000 USP units, and amylase 180,000 USP units<br>|
| Placebo Comparator: Placebo<br>Subjects will be provided placebo and advised to take it with meals and snacks to provide. | Other: Placebo<br>* Placebo will be given to the patient in single blind fashion with the subject unaware but PI aware of study drug assignment from week 8-12. Placebo tablets will be given with meals and snacks similar to CREON to maintain patient blinding to study drug assignment. A follow-up visit on week 10 to review patient tolerance, side effects and possible drug adjustment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Hypoglycemia | The effect of DIET, CREON and PLACEBO on the number of hypoglycemic events (i.e. <70 mg/dl) will be assessed using a standard blood glucose monitor that measures glucose in venous blood. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Glucose Monitoring using the Medtronic iPro 2 | The effect of DIET, CREON and PLACEBO on the percent of time iPro 2 glucose values are less than 70 mg/dL will be measured. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Roux-en-Y gastric bypass, Hypoglycemia, Creon