Responses to Initial Review 
Appendix B 
RAC Application 
Kenneth L. Brigham, M.D 
PRINCIPAL INVESTIGATOR: Kenneth L. Brigham. M.D. 
TITLE OF PROPOSAL: Expression of an Exogenously Delivered Human Aloha- 1 Antitrypsin Gene in the Lungs 
ITEM #3: The discomforts, inconveniences and/or risks that can reasonably be expected are: 
The bronchoscopy necessary to put the material in your lung will be like the one you had earlier to 
determine what was wrong with your lung, except much briefer in duration and no pieces of tissue or other samples 
will be taken. You will be given a mild sedative and your nose and airway will be numbed with medicine to make 
it as comfortable as possible. The bronchoscopy will be performed in the outpatient surgery department of The 
Vanderbilt Clinic. Bronchoscopies are routinely done in this location and the outpatient surgery department is fully 
equipped to handle bronchoscopies. The bronchoscopy itself should take no more than 45 minutes to perform. 
Following bronchoscopy, you will be observed in the outpatient recovery room for approximately 3 hours. 
Bronchoscopy is a safe and simple procedure. Because no pieces of tissues will be taken, the risks involved 
are even less than most routine bronchoscopies. Your blood pressure, heart rate, and the oxygen in your blood will 
be monitored throughout the procedure. There is an very low risk of serious bleeding when a bronchoscopy is done. 
We screen for bleeding abnormalities and because no pieces of tissues are taken, bleeding complications are 
unlikely. In your case, this risk will be less than 0.1%. Some individuals may experience a fall in the amount of 
oxygen in their blood. Again this is unlikely. We will monitor the oxygen in your blood and give extra oxygen as 
necessary. Occasionally, a collapsed lung occurs following bronchoscopy. This event is almost universally 
associated with obtaining pieces of tissue which we are not going to do. Other less common complications include 
pneumonia following bronchoscopy and irregular heart rhythm. Rarely, it is possible that the discomfort of the 
procedure or one of the drugs given will cause a reaction. Coughing is associated with bronchoscopy. Whenever s 
coughing is encountered we administer medicine to stop the cough. 
The possibility of any complication occurring from the bronchoscopy is less than 1%. ■ ; 
There is no reason to believe that the DNA/lipo^Ome mixture should cause any problems for you. There i 
is no risk that the DNA itself or the liposomes would cause any kind of infection or cancer. We know of no side i 
effects of putting DNA or liposomes into your lungs. Even though the material will be put into the lung which will | 
be removed, it is possible that some of the DNA or liposomes will be absorbed and go to some other organ like the i 
liver. Should this occur, we have no reason to believe that it would cause any side effects. ] 
If you are a woman of reproductive age, a pregnancy test will be required to document that you are not j 
pregnant. In addition, contraception is required for one month prior to the study and for two months following I 
the study. This is strictly a safety precaution. Studies in animals given DNA/liposome mixtures have not detected || 
any of the delivered DNA in reproductive organs. j 
The possibility that this bronchoscopy will result in a delay in your surgery is extremely low, less than the ' 
possiblity of a complication from the bronchoscopy. Our study will be conducted in conjunction with your surgeon } 
and will be coordinated according to what is the best schedule for you. If, by some very unusual circumstances, i 
the bronchoscopy should delay your surgery, a short delay would not alter the overall outcome or prognosis of your ' 
medical condition. 
NOTE: Immediate necessary care will be provided without charge by Vanderbilt University if you are injured ^ 
because of participation in this research project. However, there is no provision for the costs of further medical 
care or for the monetary compensation for such injury. 
ITE.M #4: The possible benefits to you from this study are: [ 
You will receive no direct benefit from this study. [ 
ITE.M #5: The benefits to science and to mankind that are sought by this study are: | 
The possibility of gene therapy is an entirely new area which may be beneficial in the large number of 
human diseases. This study is a first step in that direction and, if successful, will pave the way for application of 
this method in patients with lung diseases like emphysema. 
ITE.M #6:(a) Alternate procedures that might be advantageous; but which will not be used are: ^ 
There are no alternate procedures. I 
(b) The reasons for not using them are: 
N/A I 
ITEM #7: Your rights of privacy will be maintained in the following manner: 
(1) AII data obtained on you during the course of this study will be kept confidential and accessible only to the 
principal investigator and his/her assistants on this project; except as stated elsewhere. ^ 
(2) Should the results of this project be published, you will be referred to only by number. j 
NOTE: YOU ARE FREE TO WITHDRAW THIS CONSENT AND TO DISCONTINUE PARTICIPATION IN THIS 
STUDY OR ACTIVITY AT ANY TIME. 
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Recombinant DNA Research, Volume 19 
