Influenza ("Flu") & Avian Influenza ("Bird Flu") Clinical Trials

Instructions: Read this document and the informed consent file found at the bottom of this page, then print them both and show them to your physician.

INTRODUCTION

Influenza, including avian influenza, appears to cause serious disease and death in patients with a normal immune response because these patients overdo their immune response to the virus. This point of view is controversial, but is becoming increasingly accepted by virologists and immunologists.

Angiotensin II appears to be an early signal in activating the immune response, and inflammation in general.

Medications which block angiotensin II have been available for over two decades. These include ACE inhibitors (ACE = angiotensin I-converting enzyme, the enzyme that converts angiotensin I—which is inactive—into angiotensin II, the active signal) and ARBs (for Angiotensin II Receptor Blockers). Nobody taking an ACE inhibitor or an ARB has ever seemed immunosuppressed, so there seems to be no down-side to this study. In other words, we don't believe that taking an ACE inhibitor or an ARB will make you MORE susceptible to death from the influenza virus.

GenoMed is pioneering the use of ACE inhibitors or ARBs for the treatment of viral diseases like influenza. We have recently published positive but very limited results for West Nile virus (see reference 1, below). We hope that we'll have similar results for influenza and avian influenza.

THE STUDY

At this early point in the flu season, we do not have enough information to know whether ACE inhibitors or ARBs will be able to prevent the flu/bird flu or just limit the symptoms of people who get the flu; both; or neither. So it will be up to you, the patient, to decide if you want to try to prevent the flu, in which case you would start taking an ACE inhibitor or ARB right away and keep taking it for the duration of the flu season, i.e. throughout the fall and winter, until spring (May 1st, let's say). You would do this if you felt that the flu was so dangerous for you that you would do almost anything to avoid getting it. This approach may help you prevent it. BUT IT MAY NOT. WE JUST DON"T KNOW YET.

If you're not that worried about how you'll do with the flu, and you don't feel that it's so important that you prevent it, then you can wait until you get it, and then try taking an ACE inhibitor or ARB to see if you get over it more quickly than usual. So the minute you feel achy, tired, start coughing up clear phlegm, or have a fever, you would go to your doctor and tell him/her about this trial. If s/he agrees, s/he will prescribe an ACE inhibitor or ARB for you. AGAIN, PLEASE NOTE: WE DON'T KNOW IF YOUR SYMPTOMS WILL GO AWAY FASTER WITH THIS TREATMENT. THAT'S WHY THIS IS CALLED A "CLINICAL TRIAL."

We'll be following you about once a month by email. You'll get the same message each month or so—basically, "How are you feeling? Have you had the flu since our last email?" If you answer yes, then we'll ask you whether you took the ACE inhibitor or ARB, which one you took and at what dose, how long the flu lasted, how long the flu usually lasts for you, etc.

The choice of whether to use an ACE inhibitor or ARB is up to your physician. If you already have high blood pressure, then we would recommend a hydrophobic ACE inhibitor such as quinapril, which will soon be generic. If your blood pressure is normal or even low, then we would recommend the smallest possible dose of one of the seven available ARBs, any one of which can be broken in half to further minimize the chance that it will lower your blood pressure too much. In other words, start low and work your way up on the dose to avoid getting dizzy or lightheaded from the ARB. You could start at half the dose recommended below, and after a day or two, if you're not feeling dizzy or lightheaded, take that dose twice a day to equal the "usual daily adult dose for a person with normal or low blood pressure."

* Usual Daily Adult Dose for a person with normal or low blood pressure.
Your doctor or primary care provider may be able to get free samples of some of these drugs from the appropriate drug representative.

ELIGIBILITY

Only people with an intact immune system are eligible for this study. People who are known to be immunosuppressed are not eligible. We do not consider children or the elderly to be immunosuppressed, and they are eligible for this study. The people whom we do consider to be immunosuppressed are those taking one of the following medications or with the following diseases (see list below).

List of immunosuppressive medications or treatmentsmaking patients INELIGIBLE for this study:

• Prednisone
• Dexamethasone
• Decadron
• Methotrexate
• Cyclosporin or FK506
• Chemotherapy

List of diseases which leave people immunosuppressed and thus INELIGIBLE for this study:

• Leukemia
• HIV or AIDS
• Organ transplants (heart, kidney, liver, pancrease) -- joint replacements are OK

You are also INELIGIBLE for this study if you have ever had an allergic reaction to an ARB. If you have had an allergic reaction to an ACE inhibitor, it is possible that you will be OK with an ARB. But trying an ARB, as in this study, is a decision that your physician will have to make.

WHAT TO DO NEXT

1. Print out these instructions and the Informed Consent Document and show them to your physician.

2. If you and your physician decide that this study is in your best interest, then sign and
FAX in the Informed Consent document to 314-983-9939 or mail it to the address
below. Your physician will prescribe the appropriate medication, either a hydrophobic
ACE inhibitor like ramipril (ALTACE), quinapril (ACCUPRIL, which is generic), or
trandolapril (MAVIK), or an ARB from the list above.

3. Contact Us at least once a month to let us know how you are doing.

Sincerely Yours,

David W. Moskowitz MD, MA (Oxon.), FACP
Chairman and Chief Medical Officer
GenoMed, Inc.
9666 Olive Blvd., Suite 310
St. Louis, MO 63132
Tel: (314) 983-9933