We are testing a new combination of medicines, to determine if they could be used to treat cystic fibrosis (CF). Subjects with CF who have two copies of the most common mutation (change) found in patients with CF called DF508. CF is caused by a lack of chloride movement in the nose, sinuses, lungs, intestines, pancreas and sweat glands. We are conducting this study to determine the safety of using a combination of two medicines, Phenylbutyrate and Genistein, to improve the ability of the cells lining the nose to regulate movement of salt (chloride) and water in people with CF.

Phenylbutyrate has been extensively used to treat patients with rare metabolic diseases (which are very different from CF), 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. Both drugs may be able to restore normal chloride movements in body organs and glands. We will be studying salt and water in the nose movement by a technique called nasal transepithelial potential difference (NPD).

Condition	Treatment or Intervention	Phase
Cystic Fibrosis	Drug: Sodium 4-Phenylbutyrate (Buphenyl)  Drug: PTI G4660 (Genistein)	Phase I

Further Study Details: 

Subjects will be randomized to receive either the Phenylbutyrate or placebo tablets for 1 week, with a 2 out of 3 chance of receiving Phenylbutyrate at a standard adult dose, with visits on study days 1, 4, and 7. The study will last an additional 2 weeks to determine whether the effects of the Phenylbutyrate or Placebo persist for any length of time, with visits on study days 14 and 21. Every participant will receive the Genistein during the NPD on days 1 and 7. The dose of Genistein used will not be escalated and will be the same for every participant.

Safety evaluations at each visit will include a history, and physical exam and mental status exam, blood and urine tests, and lung function tests. The main physiologic outcome of the trial will be the assessment of salt and water transport NPD. In this way, we will assess whether genistein enhances the effect of phenylbutyrate to improve chloride transport in the nose by topical application of genistein to the nasal mucosa during the NPD procedure on study days 1 and 7.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

a) All ethnic groups b) Females and males c) 18 years of age or older d) 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. e) Willing to practice a reliable and study-accepted method of contraception during the study Acceptable methods are abstinence, barrier methods, or oral contraceptives. (This is predominantly directed at female subjects, as males with CF are typically sterile due to obstructive azospermia. We will encourage males to use barrier methods for the duration of the study on the small chance that fertility exists). f) Diagnosis of cystic fibrosis consisting of both: - sweat sodium or chloride > 60 mEq/L by the pilocarpine iontophoresis method and cystic fibrosis genotype homozygous for DF508-CFTR - clinical manifestations of cystic fibrosis h) Oxyhemoglobin saturation ? 92% while breathing room air

Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting

Study ID Numbers:  NCRR-M01RR00240-1765
Record last reviewed:  December 2003
Last Updated:  March 25, 2005
Record first received:  May 31, 2001
ClinicalTrials.gov Identifier:  NCT00016744
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08