Phenylbutyrate/Genistein Duotherapy in Delta F508-Heterozygotes (for Cystic Fibrosis)

• Status: Terminated
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research study is to test a new combination of medicines, Phenylbutyrate and Genistein, to determine if they could be used to treat cystic fibrosis (CF). The most common genetic mutation found in patients with CF is called Delta F508. Due to this mutation, there is a lack of salt (chloride) movement in your nose, sinuses, lungs, intestines, pancreas and sweat glands. This lack of movement causes the clinical manifestations of the disease.

Although Phenylbutyrate has been extensively used to treat patients with rare metabolic diseases, Phenylbutyrate is an investigational drug for the purpose of this study. Genistein is a naturally occurring substance that is found in food products such as soy and tofu, but is also an investigational drug for this study. When used together, both drugs may be able to restore normal chloride and salt (water) movements in body organs and glands in people with CF.

We will be studying salt and water movement in the nose by a technique called nasal transepithelial potential difference (NPD).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborators: Cystic Fibrosis Foundation; Cystic Fibrosis Foundation Therapeutics
• Treatments: 4-phenylbutyric acid; Genistein

Criteria

Inclusion Criteria:

1. Able to communicate with pertinent staff, able to understand and willing to comply with the requirements of the trial, and able and willing to give informed consent.

2. Willing to practice a reliable and study-accepted method of contraception during the study.

3. Diagnosis of cystic fibrosis consisting of both:

1. clinical manifestations of cystic fibrosis and

2. either cystic fibrosis genotype heterozygous for Delta F508 with a second identified CFTR mutation, or cystic fibrosis genotype with one Delta F508 allele and one unidentified allele and sweat sodium or chloride > 60 mEq/L

4. Oxyhemoglobin saturation greater than or equal to 92% while breathing room air

Exclusion Criteria:

1. Underlying diseases likely to limit life span and/or increase risk of complications:

1. Cancer requiring treatment in the past 5 years, with the exception of cancers that have been cured, or in the opinion of the investigator, carry a good prognosis such as non-melanoma skin cancer, papillary thyroid carcinoma, and cervical cancer in situ.

2. GI disease

i. Inflammatory bowel disease requiring treatment in the past year ii. elevations in ALT or AST levels to greater than 3 times the upper limit of normal

2. Conditions or behaviors likely to affect the conduct of the study

1. Current or anticipated participation in another intervention research project

2. Recent (with 2 months) sinus surgery or nasal polypectomy

3. Currently pregnant or less than 3 months post-partum

4. Currently nursing or within 6 weeks of having completed nursing

5. Unwilling to undergo pregnancy testing or to report possible or confirmed pregnancy promptly during the course of the study

6. Unwilling to use a reliable contraceptive method for two months after the completion of the study.

7. Major psychiatric disorder, which, in the opinion of the investigators, would impede conduct of the study, e.g., alcoholism

8. Other condition, which, in the opinion of the investigators, would impede conduct of the study.

3. Glucocorticoids other than topical, ophthalmic, and inhaled preparations.

4. Conditions that would place the patient at an increased risk for complications:

1. Pneumothorax within the last 12 months

2. Uncontrolled diabetes

3. Asthma or allergic bronchopulmonary aspergillosis requiring systemic glucocorticoid therapy within the last two months

4. Sputum culture growing a pathogen that does not have in vitro sensitivity to at least two types of antibiotics which could be administered to the patient

5. History of major hemoptysis: (Greater than 240 mL of blood within a 24-hour period within the last 12 months).

5. Medication use or conditions not specifically mentioned above, including severe or end stage CF lung disease, that may serve as criteria for exclusion at the discretion of the investigators.

6. History of significant cardiovascular disease, such as myocardial infarction, congestive heart failure, unstable arrhythmia, or uncontrolled hypertension.