M.J. Welsh and A.E. Smith, RAC Application 
Ad2-ORF6/PGK-CFTR 
Item 5 - Clinical Protocol 
Measurement of Voltage Across the Sinus Epithelium. 
Measurement of the transepithelial electrical potential difference across the sinus epithelium should not 
produce significant discomfort; it is well tolerated in the nasal epithelium. The drugs applied topically 
during the course of the study have no significant local or systemic effects. 
Application of Ad2-ORF6/PGK-CFTK. 
Placement of the indwelling catheters in the maxillary sinuses 7 days before vector administration could 
produce discomfort There may also be minor discomfort from having to remain still during the 
procedure. These discomforts should be minimized by local anesthesia with topical 2% lidocaine to the 
nasal mucosa and by administration of Midazolam 1-2 mg. IM shortly before applicauon. The major 
risks of lidocaine and Midazolam would be hypersensitivity which is very rare. The Midazolam could 
theoretically produce some respiratory depression; however the dose we will use should have no 
significant effects, particularly in these subjects who will only have mild to moderately severe disease. 
There is also the risk of minor bleeding at the site of entry into the maxillary sinus. Lavage of the 
maxillary sinuses could cause discomfort. On subsequent applicauon of virus the participants may 
experience similar discomfort. During the week before the first administration of vector the participants 
will be treated with IV antibiotics. The specific antibiotics will be chosen based on the culture and 
sensitivities of the sputum and nasal/pharyngeal swabs. We will monitor blood levels of antibiotics and 
adjust the doses appropriately. Such treatment is common for patients with CF. 
Biopsy of the Maxillary Sinus Mucosa. 
Biopsy of the maxillary sinus epithelium will produce mild to moderate pain and discomfort. Pain and 
discomfort during the procedure will be minimized by use of local anesthesia. Subsequent use of 
analgesics will be allowed if needed. A small risk of bleeding or subsequent scar formation after the 
biopsy is possible as is expected for such a routine procedure. 
Sinus Computed Tomography. 
Sinus CT carries the risk of radiation exposure; we anticipate that a subject will have one sinus CT, and 
up to 8 limited cut CTs of the maxillary sinuses during the course of the studies. Although there are no 
known adverse effects for this amount of radiation, the long term effects of such radiation are not known 
with certainty. 
Potential Benefits. 
The potential benefits are described in Part A of this protocol. 
OTHER ISSUES 
Confidentiality. 
Confidentiality will be maintained throughout the study. Publication of results will not identify the 
patients. Genzyme Corporation agrees to maintain confidentiality. 
Compensation to Participants. 
Participants will be compensated for the time and inconvenience involved in participating in the research 
in the amount of $75 for each day spent in the hospital. In addition, we will reimburse them for their 
travel expenses to and from the University hospitals at a rate of $0.25 per mile and for parking expenses. 
No additional costs to the subject are anticipated as a result of participation in the study. 
REFERENCES I 
1. Boat, T.F., M.J. Welsh and A.L. Beaudet. 1989, Cystic Fibrosis. In: The Metabolic Basis of Inherited 
Disease , C.R. Scriver, A.L. Beaudet, W.S. Sly and D. Valle. editorsMcGraw-Hill, Inc., New York, 
NY: p. 2649-2680. 
2. Taussig, L.M. 1984. Cystic Fibrosis, Georg Thieme Verlag Stuttgart, New York: 
3. Collins, F.S. 1992. Cystic Fibrosis: Molecular Biology and Therapeutic Implications. Science 
256:774-779. 
4. Mulligan, R.C. 1993. The basic science of gene therapy. Science 260:926-932. 
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