Alzheimer’s Prevention Research Study

[Dora]

I was informed last week that the Generation 1 and 2 studies have been closed due to negative findings with the medication. The whole study has been closed- even for those in process of getting results for some tests done. Dora

[DebS]

I was informed last week that the Generation 1 and 2 studies have been closed due to negative findings with the medication. The whole study has been closed- even for those in process of getting results for some tests done. Dora

Hi Dora,

Thanks for posting the update to let everyone know of this news. If you are looking for other studies and ways to support research, you may find our Wiki page on ApoE4 Research helpful. If you haven't yet discovered our primer of information and prioritized steps to consider, you may also find that valuable.

Please feel free to reach out with any questions.

[NF52]

I was informed last week that the Generation 1 and 2 studies have been closed due to negative findings with the medication. The whole study has been closed- even for those in process of getting results for some tests done. Dora

Welcome, Dora!
We're glad you found this site, and assume you have some interest in either the Generations Studies or in clinical trials being done with observations and/or interventions to prevent cognitive decline. If so, you're at the right place! Here's a link to a recent series of posts about this topic, from some of us on the site who are currently enrolled in either Generations 1 or 2 CAD106 and CNP520

Generations 1 was for people with ApoE 4/4 and includes two "arms"; one comparing an immunotherapy drug called CAD106 delivered by shot once every 7 weeks vs. a placebo shot. and the second comparing a BACE-1 inhibitor class of drug called CNP520 take as a 50 mg. oral pill daily versus a placebo pill. I know someone who was randomly assigned to the CAD106 shots; she has been told that while they are not enrolling any new participants, they are also (as of now) NOT ending that study. That drug is a different mechanism that CNP520 and in earlier trials showed safety in removing amyloid plaques from the brain.

Generations 2 was for people with either ApoE 3/4 or 4/4, and participants were randomized to either a placebo vs. 15 mg. dose of CNP520 or a placebo vs. 50 mg. dose of CNP 520. The reasoning behind the lower dose was that, of successful in preventing cognitive decline, a low dose might be more effective if given at a younger age and also safer.

I am one of the Generations 1 CNP520 or placebo participants, and while they told us to stop taking the pill as of earlier this month, the study is not completely wrapping up for about another 9 months. First, all of us will have our next scheduled series of cognitive, motor, daily living and behavioral tests and questionnaires, along with regularly scheduled blood and urine tests and an EKG. Mine will be in Sept; I know of someone else who had hers today. Six months after our "test day" each person will have a final study visit with no cognitive tests but a planned MRI and PET scan, I think. In my case that will be next March, the 2.5 year mark of what was going to be a 5-yr study.

The researchers have an enormous amount of information, which they have promised to share with other researchers once the study is complete and the data is de-identified. In addition, after all participants have finished the study, which I assume will be around April 2020, they will let us know whether we were in the CNP520 or placebo group. I have always been able to get the results of my blood tests, which I share with my primary care provider and I have gotten the general results of the MRI, which I believe is also true for other participants. I have not gotten the PET scan results which would show whether I have amyloid deposits, or if they have changed over time, since that would probably also alert me that I was on the actual study drug and they want people to stay "blinded" to their assignment until everyone is done.

As for the "negative findings": We will also get more information about that. I believe some will come at my next visit and probably more after the study has completely ended and more data is analyzed.

What I know from the study site now is that based upon results reported last October by two other drug trials using a BACE-1 inhibitor. Those studies both ended when outside, independent data evaluators (who can see "un-blinded data" showing who get the drug and who gets the placebo) found subtle cognitive decreases in some participants receiving the study drug at 3-month or 6-month testing during the first year of those drugs' trials. That had not been seen in the Generations Studies, but they decided to add further testing at the 3-month point (previously participants were tested on the baseline day-when they started the pill/placebo or injection/placebo) and then every 6 months.

At the first evaluation of that additional testing in January, and again I think in March, the outside evaluators found no differences. In the late June 2019 outside data monitoring, they did see a change. Like the other studies, it apparently only happens with some people (no info on what percentage, or any common factors in that group) and the decrease does not appear to get worse over time. (That's puzzling to me; since when I get poison ivy, it's definitely worse if I'm dumb enough to spend an hour and not just 15 minutes wrangling poison ivy!)

So with that LONG explanation, I hope I have answered some questions you might have had. Feel free to share if you or someone you know was affected by this, and what your feelings around the process have been. We have about 10 people that have mentioned being in Generations 1 or 2 on the forum, and others who were screened and for one reason or another were either ineligible or chose not to participate.

And as a guide to finding your way around this site, the "How-To" Get the most out of the ApoE4.info website will save you time--and aggravation, I hope!

Hope your user name "Dora" means that you have a lovely name or that you have a lovely name and are also an eager "Dora the Explorer" of new information and ideas that help you guide your path in life.

[Dora]

Thanks. I was eligible for the Gen study and had some testing done in early June. However, just got a call last week that they were not continuing the study at that site, and no one who had testing done would be getting any results. I am glad those who have had more extensive testing will be able to get continued follow up. Disappointing as I was looking forward to participating in it. I will continue to BOLO for other clinical trials.

Thanks for the welcome. I have been reviewing the information on this site for a while and found it very helpful.

[donbob]

...no one who had testing done would be getting any results...

The disclosure documents specify test results to be provided. I had an appointment after the cancellation with our site principal investigator. He provided me with a document with my PET scan result.

[NF52]

Thanks. I was eligible for the Gen study and had some testing done in early June. However, just got a call last week that they were not continuing the study at that site, and no one who had testing done would be getting any results. I am glad those who have had more extensive testing will be able to get continued follow up. Disappointing as I was looking forward to participating in it. I will continue to BOLO for other clinical trials.

Thanks for the welcome. I have been reviewing the information on this site for a while and found it very helpful.

Hi again, Dora.
The first part of the screening includes a meeting to go over information on ApoE4 and then to get your consent to disclose your ApoE4 status, if I remember correctly. That is followed by some initial screening testing of cognitive skills to be sure people meet the requirement to have overall skills within normal limits for their age at the time of baseline (i.e. not mild cognitive impairment or early stage dementia) and to rule out health or other factors that would not allow them to participate safely. After that comes the other initial tests (MRi, PET scan, blood work, etc. (again relying on memory here) with the "official" baseline testing on the day you start with the assigned "study drug" (whether real or placebo, which neither you nor the study site would know.) It's possible that if you didn't get to the baseline date that they feel there is no usable data to share; however, I would encourage you to call your contact person at the Study Site and ask for it anyway. They should have given you a list of names on the consent form, including the Study Doctor overseeing Generations at your site, and someone who serves as a sort of ombudsman if you have concerns. You may want to give one or both of those people a call anyway.

I am not sure that I will get the results of all my cognitive tests, which is okay with me. I have a sense of what I did okay on and what I didn't (I draw as well as the average 10 year old--on a good day--something that hasn't changed in the last half-century!)

I think it's great that you are on the lookout for other studies! The Clinical Trials.gov website has great information on LearningAbout Clinical Studies which explains what types of studies are done, what to ask before participating and what protections participants have. In addition they have an Clinical Trials: Advanced Search page that allows you to search by your locality and by topic (ex. Alzheimer's) and other criteria (recruiting, not yet recruiting, by age, by observational or interventional studies). The listings can then be looked at individually; I always recommend reading the provided information carefully. Just because a study is listed on the website does not mean it's receiving federal funding, or is posing a reasonable research question and has the size study and time length to find answers.

Glad you've been enjoying the site!

[Elevation]

Generation 1 Study. I was admitted to the Generation 1 Study and had been taking either the drug or a placebo for about 3 three months. I received a phone call a few weeks ago and was told that the research program has been closed due to adverse side effects. I believe that this closure is nationwide but because I haven't seen any other postings, I am wondering if it is just the center where I was enrolled. Has anyone else been told about the program being shut down?

[NF52]

Generation 1 Study. I received a phone call a few weeks ago and was told that the research program has been closed due to adverse side effects. I believe that this closure is nationwide but because I haven't seen any other postings, I am wondering if it is just the center where I was enrolled. Has anyone else been told about the program being shut down?

Hi Elevation,
The arm of Generations 1 with CNP520 and Generations 2 which included 2 different doses of CNP520 versus a placebo, have both been stopped completely with most people notified around July 11. I’m not sure why your study site didn’t call or email you then to stop taking the pills you had.
The decision was made after independent evaluators, who are able to see the results of people taking a study drug during the study, found that some participants who were getting CNP520 showed a reported mild decrease on some, but not all cognitive tests at either 3 or 6 months after starting the drug. They don’t yet know what caused that, and those people didn’t show continued drops at later dates apparently. But since other clinical trials with similar drugs also found this side effect, it is assumed to be an effect of the drug type (BACE-1 inhibitors).
Each site will bring people back for their next round of cognitive assessments and may be asking us to get a last MRI. Then, 6 months after that, we will have a final appointment, at which I assume they will tell us whether we were on the placebo or CNP520 and any plans for continued follow-up.
I would encourage you to call your contact person at your site, who may be the Nurse Practitioner, or Study Coordinator and ask whatever questions you have about your particular schedule and the delay in letting you know this news.
Hope this helps for now. Don’t take any more pills; just hold onto the bottles and take them all back to the next visit.