Short Term Safety and Efficacy of Lubiprostone in Adults With Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to determine the short term safety and effectiveness of lubiprostone when used for constipation in adults with cystic fibrosis.

Detailed Description
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Cystic fibrosis (CF) affects about 30,000 people in the United States. It is caused by an absent or dysfunctional protein called CF transmembrane conductance regulator (CFTR) which functions as a chloride channel. Lubiprostone is a medication indicated for constipation that activates type 2 chloride channels (ClC-2) and has the potential to be an effective treatment for constipation in adults with CF. It has the potential to correct the underlying disorder by utilizing a chloride channel whose activity does not depend on CFTR. This project is a prospective open-label pilot study to examine the safety and effectiveness of lubiprostone when used in adults with CF with constipation. The specific aims are as follows: 1) Determine the effectiveness of lubiprostone for constipation in participants with CF, and 2) Determine the short term safety of lubiprostone in adults with CF. Data will also be collected to generate further information about the effect of lubiprostone on nutritional status.

Official Title
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Short Term Safety and Efficacy of Lubiprostone in Adults With Cystic Fibrosis

Conditions
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Constipation, Cystic Fibrosis

Intervention / Treatment
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* Drug: lubiprostone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women of all races 18 years of age or older at time of enrollment Diagnosis of cystic fibrosis History of constipation, as defined by the Rome III criteria, OR the requirement of chronic scheduled doses of a laxative, OR a score ≥1.5 on the Patient assessment of constipation symptoms (PAC-SYM)15 survey administered during the screening visit, OR a score of less than 3 on the Bristol Stool Scale (BSS) at the screening visit. Exclusion Criteria: Current gastrointestinal (GI) obstruction History of GI obstruction requiring hospitalization within six months of enrollment Pregnancy or breastfeeding Hypersensitivity to lubiprostone or any of its components Serum creatinine >1.8 mg/dL at last annual visit Clinically significant liver disease, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3X upper limit of normal History of frequent hospital admissions for CF exacerbations (≥4 in the last 6 months) Currently registered on a lung transplant waiting list Women of capable of child-bearing who either refuse a pregnancy test, or are incapable or unwilling to use contraception during the protocol, or both. Any other condition, in the opinion of the investigators, that interferes with the ability of the participant to comply with study requirements, confers significant risk to the participant, or limits the ability of the participant to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: lubiprostone|lubiprostone 24 microgram capsule taken twice daily for 4 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Spontaneous Bowel Movements Per Week |  | 2-week run-in period, 2-weeks of treatment, 4-weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Assessment of Constipation Symptoms | The Patient Assessment of Constipation - Symptom (PAC-SYM) survey is a 1-page 12-item tool that measures a patient's assessment of constipation symptoms. The items are in Likert scale format and address the severity of stool, rectal and abdominal symptoms over the past 2 weeks. Items are scored on a scale of 0 to 4, with 4 indicating the most severe. To compute the overall score, the scores of the non-missing items are summed and this is divided by the total number of non-missing items (overall score range, 0 to 4). | 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment | 
| Bristol Stool Scale Score | The Bristol Stool Scale is a scale used to rate the consistency of stool. Stool types are accompanied by a written description. There are seven types of stool that are scored from 1 to 7. A score of 1 or 2 indicates constipation; a score of 6 or 7, diarrhea. | 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment | 
| Body Mass Index |  | baseline, 2 weeks of treatment, 4 weeks of treatment | 
| Self Reported Adverse Effects at Each Study Visit | Adverse effects are problems reported by each study subject that they experienced during this clinical trial. Examples are headache and nausea. Study subjects were asked at each visit while on study drug to report any adverse affects that had occurred since the last visit. | During entire study period | 
| Serum Sodium |  | baseline, 4 weeks | 
| Serum Chloride |  | baseline and 4 weeks | 
| Serum Potassium |  | baseline and 4 weeks | 
| Serum Bicarb |  | baseline and 4 weeks | 
| Serum BUN |  | baseline and 4 weeks | 
| Serum Creatinine |  | baseline and 4 weeks | 
| AST |  | baseline and 4 weeks | 
| ALT |  | baseline and 4 weeks | 
| Serum Calcium |  | baseline and 4 weeks | 
| Serum Magnesium |  | baseline and 4 weeks | 
| Serum Phosphate |  | baseline and 4 weeks | 
| Serum Glucose |  | baseline and 4 weeks | 
| Serum Vitamin D |  | baseline and 4 weeks | 
| Serum Vitamin A |  | baseline and 4 weeks | 
| Serum Vitamin E |  | baseline and 4 weeks | 
| Serum Prealbumin |  | baseline and 4 weeks | 
| Serum Albumin |  | baseline and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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constipation, cystic fibrosis, lubiprostone, Constipation in adults with cystic fibrosis