RE: PSC/urso trial

[Guest guest]

, (who also lives

in Seattle) is already

in the trial. Hang in there, he’ll

answer soon.

-Barb in Texas - Son Ken (30) UC 91 & PSC 99

PSC/urso

trial

I have been asked to join the high-level urso

trial that's being

sponsered, in part, by the Mayo clinic. I

have a doctor at the

clinic itself and another here in Seattle, and at

first this trial

thing really sounded good...do something with my

disease, help

others, etc. But then last night I read the

release form and it

scared the crap out of me - it sounds like they

don't pay for

anything, I have to go through lots more testing

than I normally

would, I have to commit to not getting pregnant

for four years, and

if I get the placebo my PSC will go untreated...so

I am undecided.

I want to help the medical community, and my disease

has been pretty

manageable so far, but I am afraid that this is a

HUGE risk, not to

mention an enormous personal sacrifice (aka the

kids thing). It

seems like they're asking a lot...

Is there anyone out there that is doing the trial

and wouldn't mind

sharing their experience with me?

[Guest guest]

Dear " regandv " ;

It's a very personal decision whether or not to participate in a

trial of this kind. We had a similar reaction to the one you describe

when our newly diagnosed son, , was asked to participate in the

high-dose trial at Mayo. He'd been on ursodiol for 1 month when asked

to participate in the trial, and he'd already seen a dramatic

reduction in his ALT and AST levels. The double-blind nature of the

trial is admirable, but since you can easily tell if you are on urso

simply by looking at your serum liver enzyme levels, it's

hardly " blind " !

would have to have gone off urosdiol for 3 months " to allow

his liver enzymes to elevate again " before starting the trial!

did not want to run the 50% chance of being on placebo for 4

years if there was any chance that it could be doing some good [we

had read, and continue to read, that ursodiol may protect against

colon cancer and biliary malignancy], and he did not want to run the

risk of losing this potential benefit. He also did not want to be

subject to the additional tests.

Here's a comment from Dr. Chapman, leading PSC researcher in

the U.K., on the future of ursdiol trials in PSC (U.K. Oxford

meeting, 2004):

http://www..demon.co.uk/page8.html

" Just a brief word on the anti-cancer effect of Urso. It was

originally noticed with PBC patients who had been on Urso that they

had less pre-cancerous colonic polyps compared with those not on

Urso. Although PBC, unlike PSC, is not associated with higher risk of

cancer of the colon. A Mayo Clinic study which I showed you last year

also produced evidence that PSC patients who had been on Urso had

less pre-cancerous changes in the colon compared with those not on

Urso. We have two groups of 80 and 40 patients under study and our

incidence of colon cancer in both groups is much lower than in the

Mayo study: perhaps because we have been using Urso for a long time.

We see a marked positive effect of Urso on the colon. There is also

study from Norway which is about to be published, which shows similar

effects.

Because of this, it's unlikely that there will be any more controlled

trials of Urso. There is one more controlled trial which is in

operation in the US, looking at high-dose Urso - a Mayo Clinic 5 year

study. But they haven't even finished recruiting yet, so it's likely

to be seven years or more before we see the results. We won't see any

more trials apart from ours because of this marked effect of Urso on

the colon. Therefore, I personally believe that people should be

taking Urso. We still don't know what dose of Urso is protective -

whether a high dose is more protective of the colon. From this point

of view the use of Urso looks much brighter. "

Best regards,

Dave

(father of (19); PSC 07/03; UC 08/03)

[Guest guest]

I am in Seattle and I am in this trial. I assume you are seeing Dr.

Kowdley for this trial at the UW. I am now approaching the two year

mark of the trial. I am surprised they are still enrolling

participants at this point.

I would be happy to answer any questions you have and feel free to e-

mail directly if you wish. To give a quick answer to your questions

however here was my thinking regarding the trial.

1. Urso has not as yet been proven to have any impact in survival

time or time to transplant in PSC. Some doctors think it may help

and others think the onlyt impact it has is on lab values. You are

right that there is a chance that for 4 years you will be taking a

Placebo. If you are convinced that Urso makes a significant

difference then perhaps the study is not for you. If, like me, you

think the jury is still out then it is much easier to take that

chance. Remember, know drug would ever come to market unless there

were people willing to test it first.

2. The reason that the study does not pay for the testing done is

that all the tests conducted are part of what would be considered

routine monitoring of PSC. In year 2 I will be having Ultrasound,

EGD, Colonoscopy, Labs, and Physical exam. These are all things that

should normally be done anyway.

3. Even though I am male I to had a problem with the pregnancy

clause. Believe it or not when they originally issued criteria it

also said men could not father a baby during this time. Knowing that

was a real possability for me and knowing that there is no real

reason to be concerned about the effect of Urso on pregnancy I

convinced them to remove that clause from the study for men. I don't

think they will make that accomodation for women since there is a

much closer relationship there. If you plan on having a baby in the

next 4 years I would opt out.

Overall the impact of the study from normal monitoring has been

minimal. It is nice to have a charted out plan for care and I think

it allows you to build a strong early relationship with the doctor

and perhaps get a little more access. Let me know if you have other

questions.

in Seattle

[Guest guest]

regandv-

If you opt out of the study, I'd be interested to hear what your

doctor suggests about taking Urso during pregnancy. I did in low

doses, and I have a healthy four year old son. If you're seriously

wanting to have children pre-transplant, then I'd discuss the timing

with your doctor before commiting to a four year window for not

having a child. My doctor said that if I was going to have a child,

then I should do it sooner than later, and I'm really glad that I

did. (I had my son when I was 28 years of age.)

Just another take on this complicated situation...

Deb in VA

AIH 1997, PSC 1998, UC 1999, Listed Ltx, MELD 19

>

> I have to commit to not getting pregnant for four years, and

> if I get the placebo my PSC will go untreated...so I am undecided.

> I want to help the medical community, and my disease has been

pretty

> manageable so far, but I am afraid that this is a HUGE risk, not to

> mention an enormous personal sacrifice (aka the kids thing).