Phenylbutyrate/Genistein Duotherapy in Delta F508-Homozygous(for Cystic Fibrosis)
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).
|Cystic Fibrosis||Drug: Sodium 4-Phenylbutyrate (4PBA) Drug: Unconjugated Isoflavones 100 (PTI G-4660, 87% Genistein) Drug: Placebo||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||A Pilot Trial of Phenylbutyrate/Genistein Duotherapy in Delta F508-Homozygous Cystic Fibrosis Patients|
- The basis of analysis for the primary outcome measure will be the comparison of data from both the standard CF NPD protocol compared to a modified NPD protocol including the perfusion of Genistein. [ Time Frame: All visits ]
- Interval history, physical and mental status examination. [ Time Frame: Every visit ]
- Laboratory Evaluations [ Time Frame: Every visit ]
- Spirometry Data [ Time Frame: Every visit ]
|Study Start Date:||September 2001|
|Study Completion Date:||October 2005|
|Primary Completion Date:||October 2005 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Subjects will be randomized to receive either the Phenylbutyrate or placebo tablets for 4 days
Every participant will receive Genistein during the NPD.
Drug: Sodium 4-Phenylbutyrate (4PBA)
The standard oral adult dose is 20g/day (tablets) for 4 days.Drug: Unconjugated Isoflavones 100 (PTI G-4660, 87% Genistein)
Every participant will be administered a perfusion of 50 MicroM of Genistein during the modified NPD procedure.
|Placebo Comparator: 2||
Drug: Unconjugated Isoflavones 100 (PTI G-4660, 87% Genistein)
Every participant will be administered a perfusion of 50 MicroM of Genistein during the modified NPD procedure.Drug: Placebo
The placebo dose will match the oral tablets in arm 1, maintaining the study blind.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00016744
|Principal Investigator:||Ronald Rubenstein, M.D., PhD.||Children's Hospital of Philadelphia|