The CFIDS Chronicle, Fall 2002
http://www.cfids.org/archives/2002/2002-4fall-toc.asp
Chronicle Q&A:
Procrit Trial Focuses on Red Blood Cells

By Mark Giuliucci

Researchers at the University of Miami are testing the effects of the drug
Procrit (epoetin alfa) on people with CFIDS. The drug, also manufactured as
Epogen, increases the body’s production of oxygen-carrying red blood cells. The
study has received substantial coverage from national media outlets this year.
As part of an ongoing Question and Answer series with CFIDS researchers, the
Chronicle interviewed Barry Hurwitz, PhD, the principal investigator in the
Procrit-CFIDS study.

Q: What is the theory behind Procrit and CFIDS?

A: Procrit was developed to treat anemia. It’s highly effective in inducing
bone marrow to produce red blood cells. Procrit has been used on two groups of
patients so far: people who have cancer and have undergone chemotherapy, and
people with kidney disease who are on dialysis. To date the medication has not
been used on CFIDS patients in a large clinical trial.

Our preliminary data indicated that many of our CFIDS patients who had
difficulty with fainting spells and light-headedness also displayed decreased
red blood cell volume. We hypothesized that the lack of sufficient oxygen supply
could be a cause for these symptoms and possibly explain the fatigue as well.
The study we’re conducting is looking at whether increasing red blood cell
volume can improve these symptoms in people diagnosed with CFIDS.

Q: Do people with CFIDS have low numbers of red blood cells?

A: We have found that 60-70 percent of people with CFIDS have low-normal, or
below-normal, red blood cell volume. This was not known before we began our
work. It’s usually missed by standard blood tests.

The test we use is called a dual tag blood volume test. It is the gold standard,
the most accurate way to measure both plasma volume and red blood cell volume in
the blood. It’s commonly done in the radiology departments at most hospitals.

It’s important for those who are wondering if they have red blood cell volume
deficit that the right test be performed. Some tests only measure the plasma
volume and estimate the red blood cell volume. Those are inaccurate. For
instance, there’s a measure called hematocrit. The percentage of red blood cells
in the blood is derived from a drop of blood, but it’s really an estimate.

Q: How is the Procrit study being run?

A: We have a randomized, placebo-controlled trial funded by the National
Institutes of Health’s National Heart, Lung and Blood Institute. Dr. Nancy
Klimas and I are the principal investigators, and we work with a team of other
medical scientists. It’s a four-year study, and we’re in year two. We want to
enroll 150 people, and we’re about halfway to that goal.

We assess individuals as to whether or not they have diminished red blood cell
volume. We also give them a complete cardiovascular workup, and take other
measures that will help us test what role the immune system might play in
influencing red blood cell volume.

The actual treatment phase lasts four months, with check-ups every two weeks.
People with low red blood cell volume are randomized to Procrit or placebo
treatment. People with low red blood cell volume who receive placebo will later
receive an opportunity to obtain the four months of Procrit treatment and repeat
the testing.

If it’s determined up front that you do not have low red blood cell volume,
you’re given a placebo. That way we can compare people who have low red blood
cell volume to those with normal blood volume levels.

The drug is administered three times a week by injection. Subjects are tested
before treatment begins and after the four months of treatment. By using daily
diaries, simple reflex tests and a tilt test we examine changes in CFIDS
symptomatology, as well as the individual’s ability to control the circulatory
system. These circulatory tests are performed because in CFIDS patients the
light-headedness and fainting typically occur when the person is in an upright
posture, suggesting a circulatory regulation problem.

Q: Is it too early to comment on study results?

A: Yes, because it’s a double-blind study. The experimenters and the subjects
are unaware of the treatment assignments until after the study is finished. Then
we’ll be able to analyze the results. Subjects are provided copies of their test
results at the completion of their testing.

Q: What is the best-case scenario?

A: If individuals are fatigued, one possible cause is a lack of oxygenation in
the blood, or an inability to transport oxygen. If you have diminished red blood
cell volume, then you have less capability to deliver oxygen to the cells.
There’s a high probability that if we’re able to increase red blood cell volume
it will diminish fatigue, assuming that fatigue is a function of the capacity to
deliver oxygen to the tissues.

Q: If it turns out that Procrit does help, how long would treatments have to
be taken for a lasting effect?

A: That’s an empirical question. First, we’ll have to determine if there is a
measurable change in people who take the drug — in fatigue levels, quality of
life, exercise fitness, ability to sustain an upright posture, and in immune
function and profile.


If there is a change, then the next question is whether the treatment has to be
maintained for a long period of time. One possibility is that restoring red
blood cell volume will have a positive effect on what’s causing the problem in
the first place. Theoretically, the treatments could end at that point. That
would be a very positive outcome, because at this time Procrit is an expensive
drug.

Alternatively, we’ll have to keep searching for the main cause for the decreased
red blood cell volume. We suspect that the immune system may be involved. That’s
why we’re taking a number of immune system measures, to find out how the immune
system might be related to the decrease in red blood cell production.

Q: Why is there such a buzz about this study?

A: The fact is that there’s no accepted treatment for CFIDS. People are
desperate to find some recognizable cause. There’s obviously a strong demand for
an effective treatment.

It is very exciting to have learned from our study so far that 60-70 percent of
people with CFIDS have diminished red blood cell volume. We did not know that
before we began the study. To me, that tells people that there’s something
really physically wrong with them. For individuals who have been told before
that it’s all in your head, that you’re malingering, the knowledge that there
are real physical changes going on is confirming for them.

Even if Procrit does not improve CFIDS symptoms, the information we’re
collecting regarding circulatory functioning and immune system interactions in
relation to fatigue will shed a great deal of light on some of the important
disease pathophysiology.

Q. How can people participate in the study?

A: We’re including individuals18-55 years of age who have been diagnosed with
CFIDS by their physicians. Participants must have no diagnosed medical history
of abnormal cardiovascular conditions, epilepsy, chronic respiratory conditions,
alcohol or drug abuse, and must not be taking prescribed medications that would
have an impact on their cardiovascular system. Participants must be willing to
be available for assessments at the study site every two weeks for a seven-month
period. They have to travel to Miami at their own expense. Qualifying people
must fill out and submit a questionnaire on our Web site,
http://www.bmrc.miami.edu/research/niaid/procrit.asp. Other questions or
comments may be forwarded via e-mail to CFSresearch@....