Indywoman wrote:Well, I am in that horrible place of sadness, fear, and panic. I am 64 years old, have 4/4 homozygous, and am considering entering a randomized double blind, placebo controlled 2 cohort parallel group study to evaluate the efficacy of CAD106 and CNP520. It is part of the Generations study. Given that these are 5 year studies, I don't know if I should commit to that long a time frame given that it might foreclose other options, nor can I find a lot on the safety of previous trials of CNP520, although there is more on CAD106.
Any advice from professionals or others who chose to do the Generations study?
Hugs from a 4/4 "sister" in Virginia, Indywoman,
I've been in that place of sadness, fear, and panic. Most of us have in one way or another, and I think almost all of us will tell you "it gets better". Part of the reason it gets better is you realize you're not alone--you have the support of this group, you probably have family support, and you have people who are working super-hard to find interventions to delay, prevent and/or ameliorate the risk factors of ApoE 4/4.
So here's some quick facts:
I'm in the Generations 1 study. [There is also a Generations 2 study which includes both ApoE 3/4 individuals (only if ApoE 3/4 volunteers are also "positive" for amyloid on a PET scan) and ApoE 4/4. Generations 2 is studying several different dosages of CNP 520 only.] About 62% of participants with get one of the two drugs, randomly assigned by the "master computer" as I think of it, and 38% will get a placebo. The people at the study site won't know which you have, hence the "double-blind" status: both you and the people you see are "blind" to what you are taking. This is the "gold standard" for an experiment.
The screening process takes a few months; they want to give you time to be sure you want to join. You will be given clear information in detailed consent forms and verbal conversations with study site staff. They are clear that you can drop out at any time, and that they will notify you if they feel that for medical or other reasons you should not continue. They also promise to notify you of any developments that might be important to you. I have found the study staff to be smart, warm, helpful and committed people. I can honestly say that I look forward to seeing them every three months! During 2 of those visits, I only have an updated physical and blood work, and get new bottles of pills. In the mid-year and end-of-year visits, I will add to that repeated cognitive tests, and some imaging tests. My husband, who is my study partner, comes on the "big day" appointments; the others I do on my own. I know of 4 other women on this site who are in the Generations Trial, from 'just starting" to "into her second year." We are ready to support each other whenever needed--even if it's only to say "why did I make the mistake of asking for classic (hard) rock for an MRI?!" One woman's study partner is a long-time close friend, the others are husbands.
Part of the reason for the 5-year trial is to be able to show conclusively whether CAD106 or CNP 520 work on a number of different possible pre-Alzheimer's events. So they do a number of different cognitive tests twice a year to look at possible subtle changes, as well as blood tests 4x/ year, as well as repeat imaging tests. The FDA recently gave guidance to drug companies that proof of efficacy using outcomes other "moved into Mild Cognitive Impairment" or "didn't move into MCI" could still result in fast-track approval of drugs, if they are significant.
My husband's first reaction was something like "Five years! What if we want to go on vacation during an appointment week?" Well, this study is nothing if not motivated to work with you to plan around your schedule, with "26 week" visits, for example, able to occur anywhere in 2-week range. For me, taking one pill a day, at a time I choose, is not a burden. I hope I have the real CNP520, but even if I'm taking a placebo for 5 years, I know that the multiple assessments, imaging and blood work will make a difference in what is known about ApoE4. And since I have 3 grown children who are ApoE 3/4, and 3 siblings who may be ApoE 4/4, this is an effort I feel great about making.
If you go to the search function (the 3 vertical dots on the upper right side, you can search for CNP 520 or for "authors" "lol", "p45va" and "mardi" who are veterans, and good storytellers!
Here are a few reports on it: RATIONALE FOR CNP520 DOSE SELECTION FOR THE PIVOTAL CLINICAL PROGRAM IN PRECLINICAL AD https://www.sciencedirect.com/science/article/pii/S1552526017331618RESULTS FROM A 3-MONTH STUDY IN HEALTHY SUBJECTS AGED 60 YEARS WITH THE BACE INHIBITOR CNP520 http://aanddjournal.net/article/S1552-5260(17)30351-5/fulltextTHE ALZHEIMER’S PREVENTION INITIATIVE GENERATION PROGRAM: EVALUATING CNP520 EFFICACY IN THE PREVENTION OF ALZHEIMER’S DISEASE http://www.jpreventionalzheimer.com/2803-the-alzheimers-prevention-initiative-generation-program-evaluating-cnp520-efficacy-in-the-prevention-of-alzheimers-disease.html
And in the "fair-time" mode: here is a link to a brief article in the Lancet from 2016 questioning enrolling healthy Apoe 4/4 subjects on the basis of genetics only, and a reply from the study's lead investigators. What are we willing to accept for preventing Alzheimer's disease?http://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(16)30054-0.pdf
Feel free to ask any questions, and to send me a Private Message if you want.
We're all with you in this new land!