RAC Application 
Kenneth L. Brigham^ M.D. 
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Responses to Initial Review 
Appendix B 
CONSENT FOR RESEARCH STUDY 
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f 
ADULT: (Patient) 
(Volunteer) 
X CHILDREN: (Patient) 
(Volunteer) GUARDIANS 
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PARENTS 
PRINCIPAL INVESTIGATOR: Kenneth L. Brieham. M.D. f 
TITLE OF PROPOSAL: Expression of an Exogenously Delivered Human Alpha- 1 Antitrypsin Gene in Nasal f 
Epithelium t 
NAME OF RESEARCH VOLUNTEER:. 
AGE: 
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TO PERSONS WHO AGREE TO PARTICIPATE IN THIS STUDY: 
The following information is provided to inform you about the research project and your participation in it. 
Please read this form carefully. Any questions you may have about this study will be answered. Please feel free 
to ask any questions you may have about this study and/or about the information given below. 
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Written form 
Oral form 
ITEM #1: Indicated below are the following: 
(a) The purpose of this study 
(b) The procedures to be followed 
(c) The approximate duration of this study 
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We want to see whether we can put the alpha 1 -antitrypsin gene into the cells of the nose of individuals with 
alpha 1 -antitrypsin deficiency in a way that the gene will produce the alpha 1 -antitrypsin protein. This has never [; 
been done in humans although we have shown that we can put genes into other animals and that the gene works ! 
and is safe. We have put genes into mice, rats, rabbits, and sheep. In all the animals we have studied, no side j 
effects or complications occurred due to putting the gene into them. The alpha 1 -antitrypsin gene normally exists ' 
in humans and helps protect the lungs from damage. In order for us to put this gene into your nose, small pieces } 
of DNA from viruses and bacteria are included. These additional pieces of DNA are just bits of DNA. They ' 
cannot cause a viral infection or a bacterial infection. There is no risk of you developing cancer from this DNA. 
To get the gene material into the nose cells, we mix it with a solution of very small fat particles called 
liposomes. Various types of liposomes have been used to deliver drugs to humans. The kind of liposome that we | 
are using have been used before to deliver DNA to individuals and no side effects or complications were seen. , 
We chose to ask you to participate in this study because you have alpha 1 -antitrypsin deficiency. In ! 
addition, because you do not normally produce alpha 1 -antitrypsin, we will be able to accurately measure the ' 
amount of protein that is produced following introduction of the alpha 1 -antitrypsin gene into your nose. Although ! 
the absence of alpha 1 -antitrypsin causes lung disease, not nasal disease, this technique allows a simple manner to 
assess how well our method of gene therapy works. 
Baseline alpha 1 -antitrypsin level in your nasal washing will be obtained. This involves washing your nose 
with less than a teaspoon of salt water. The nasal wash is simple to perform. The salt water will be drawn up into 
a syringe and a small tubing will be attached to the end of the syringe. The free end of the tubing will be inserted 
approximately one inch into one side of your nose. After the tubing is placed in your nose, you will place your ; 
chin to your chest, block your nose with either your free hand or with nose clips, and infuse the salt water into I 
your nose. After infusion, the salt water will be collected into a tube by gravity drainage. 
After we establish your baseline alpha 1 -antitrypsin level in the nasal washing, we will infuse some DNA |! 
mixed with liposomes into your nose. The amount of material which we will infuse is small. We only want to see i 
whether this method works in nasal cells. This entire procedure should require no more than thirty minutes. 
After the gene is put in your nose, we will obtain nasal washings and nasal scrapings three days, five days, | 
and seven days after we have given you the gene. To obtain nasal scrapings, we use a small sterile instrument that i* 
gently removes some of the cells from the lining of your nose. Nasal scrapings will allow us to obtain further 
documentation that the gene is working. la 
CONTINUED NEXT PAGE--- |i 
[1961 
Recombinant DNA Research, Volume 19 
