[badboy99]

http://www.urmc.rochester.edu/news/s...ex.cfm?id=4042

[johnt]

There's two ways of looking at the regulatory process:

Black and white: a drug is never to be used until it is approved by the regulator to treat named illnesses.

Shades of grey: the regulatory process produces information, which added to personal data suggest that the drug should or should not be used by a particular person.

The article pointed to in post 1 states:

"Isradipine is a Food and Drug Administration-approved drug to treat high blood pressure. Researchers suspect that the drug may also be effective in treating Parkinson’s for a couple reasons. First, population scale studies have shown that people taking the drug for high blood pressure have a lower incidence of Parkinson’s disease. Additionally, isradipine is in a category of drugs called calcium channel blockers, meaning they inhibit certain cellular functions. Researchers speculate that overactive calcium channels may play a role in the death of the dopamine producing cells in the brain that is one of the hallmarks of Parkinson’s."

Those people who see things in shades of grey and are using other drugs to treat high blood pressure may wish to discuss with their doctors moving to isradipine. It can be argued both ways whether this is an off-label use.

Many PwP have low blood pressure. Does this preclude using isradipine? Or, can a second drug be added to raise BP enough to off-set the decrease caused by isradipine? This sounds perverse, and may, indeed, be perverse. It is contingent on your assessment of the risks of PD against those linked to high blood pressure.

John

[Tupelo3]

Originally Posted by johnt

Those people who see things in shades of grey and are using other drugs to treat high blood pressure may wish to discuss with their doctors moving to isradipine. It can be argued both ways whether this is an off-label use.

John

The news about Isradipine is in no way new. The relationship between the drug and lower incidence of PD has been around for over a decade. There has now been pre-clinical mouse data that supports they hypothesis of neuroprotection. In addition, conceptually, it makes sense. The announcement is for the start of the first human studies to actually test the drug for neuroprotection.

I think your suggestion about discussing it with your doctor for possible off label use is a good one. I had that conversation with my doctors (both MDS and Cardio) last year. I would suggest, however, that you keep the following in mind:

1. To date, there has only been a correlational relationship between use of the drug and lower incidence of PD (similar to tobacco and coffee). This in no way means the drug can slow or stop progression.
2. You do not know what the dosing schedule of the study will be. My understanding is that they used a much stronger dosage in the pre-clincal study than would normally be prescribed for high BP. I highly doubt any doc would recommend going over the prescribed dosage off label.
3. If it actually does work, you may not even realize if for years. Keep in mind this is not for symptom control, its supposed to be neuroprotective. So, you wouldn't normally expect immediate or short term symptom relief. What you might expect is gradual improvement or longer term stabilization. I think the study goes on for three years.

That all being said, it is certainly worth having the conversation with your doctors. Or, since this is going to be a large multi-centered trial, people should consider joining the study and getting the proper dosage (if your not a placebo) along with ongoing, continuous monitoring.

As you stated, John, PwP do not want to be playing around with their BP without proper monitoring. This may be a reason to join the study rather than try it on your own. There will be some unique approaches to offsite patient monitoring. Carematix will support clinical trial operations including data management and real time uploading of blood pressure readings from patients at home. Verizon Enterprise Solutions will provide the communications technology that enables the exchange of data so that patient information can be securely transmitted to researchers for analysis and interpretation.

Gary

[lab rat]

I've been on 10mg of isradipine for 2 years. As Tupelo3 points out, this is not a new finding. You can find several PD blogs with personal experiences using isradipine.... not many report a noticeable change in progression.

I think you will find that 10mg is a small dose.

Up until 2012, isradipine was available in continuous release form (DynaCirc CR) and, in my opinion, was more effective in PD.

I do think stadard isradipine has a very mild positive effect in PD. And, no, I have no proof.

I do have slightly high blood pressure, which isradipine fixes... if it slows my PD, that's a bonus.

[lurkingforacure]

We tried isradipine several years ago and it did nothing for us, I hate to report. We did not have any issues with blood pressure before, so we were worried it might cause some issues in that area, but felt the risk was worth it if it helped with the PD. We could not tell any difference after a year+ on it, so stopped using it.

I think since this drug has been out for so long and the news is not new, there are many white ratters who would have been heralding its praises if it really helped in the PD dept.

I'm glad if some PWp report relief from PD symptoms from this drug, but to me it just seems like it's another shady case of grasping at straws to increase revenues.

[soccertese]

Originally Posted by lurkingforacure

We tried isradipine several years ago and it did nothing for us, I hate to report. We did not have any issues with blood pressure before, so we were worried it might cause some issues in that area, but felt the risk was worth it if it helped with the PD. We could not tell any difference after a year+ on it, so stopped using it.

I think since this drug has been out for so long and the news is not new, there are many white ratters who would have been heralding its praises if it really helped in the PD dept.

I'm glad if some PWp report relief from PD symptoms from this drug, but to me it just seems like it's another shady case of grasping at straws to increase revenues.

lurking, it's an old generic so i assume not a lot of money for anyone, not even researchers.
it does bring up how difficult it is to provide neuroprotection after PD is visually detected, might be too late. that's why detecting pd or genes that increase your chances of pd as early as possible is so critical. i've read everyone would get pd if you lived long enough since we lose 1-2% of dopamine producing neurons naturally, so if you had one event that damaged a lot of neurons or somehow have a damaged system for repairing neurons you'll get pd "sooner".

lots of things have been tested to try to stop progression, CO-Q10, vitamin C, vitamin E, selegeline, i remember reading how when mirapex came on the market it was tested for neuroprotection - sinemet was thought to slow progression. TEVA is certainly making a fortune on the neuroprotection hope.

[Tupelo3]

Keeping in mind that this was primarily a safety study and only looked at efficacy as a secondary outcome, here is a summary of the Phase II trials:


FINAL OUTCOME

STEADY-PD successfully completed enrollment of 99 subjects at 21 sites over 13 months. The tolerability of isradipine was dose-dependent. Isradipine 10 mg daily dose was the maximally tolerable dosage. The most common adverse events were dosage-dependent peripheral edema and dizziness. While there was no difference in efficacy between treatment arms, the effect size compared to placebo did not rule out possible meaningful clinical benefit. Isradipine had no PD symptomatic effect based on the wash-in or washout analyses. The data supports the use of 10 mg dosage for the future efficacy trial.

There was no symptomatic benefit. However, as I previously posted, you wouldn't necessarily expect anything different if the drug does have neuroprotective potential.