macular degeneration, macular, diagnosis clinical trial – My Macular Degeneration Journey/Journal

Tag: clinical trial

Lab Rats Unite!

Hi! Long time, no write much; I know. I have, however, been lurking in the background and Lin has been keeping me apprised of some of what is happening. Certainly not all, but some.

Some of what she has said involves Facebook members and clinical trials. You guys rock!

Lin told me one member has been patiently/impatiently waiting for a trial with LumiThera. That was the page I just did “on assignment”. The one on photobiomodulation.

Lin also told me a member was being recruited for a clinical trial using stem cells. The member thought of me – and my obsession with stem cell research – and wondered why I was not being included. After all, one of the sites is Philadelphia.

First of all, I want to thank the member for thinking of me. The way we are going to get this stuff beat is to all work together both sharing and advancing knowledge. I am feeling that our time has come and the research is advancing quickly. This is because thousands of people like us are willing to be “lab rats” to get the job done.

Secondly, I want to address his query as to why the stem cell obsessed old lady is not beating down doors to get into this study. A big reason is this: they don’t want me!

I agreed to do the APL-2 study several months ago. I have integrity and am good to my word. Also, clinical trials most often look for treatment naive subjects. That means you cannot have been in any other study.

Another reason is my eyes are not bad enough. This is a phase 1 study and the best corrected acuity for this study is 37, pretty impaired.

Phase 1? A quick review here: phase 1 studies are for safety and tolerability only. Are you going to have something really weird happen? What are the reactions to this procedure and can we put up with having those reaction? Any effect achieved is gravy. We look for the effects when we do phase 2 which is a “proof of concept” phase.

Now 37 as a measure of acuity had me a little stumped. I am used to the ever popular 20/xxx notation. That is you can see at 20 feet what normal eyes can see at xxx feet.

Precision-Vision.com published a handy dandy little Visual Acuity Ranges and Visual Acuity Notations chart. The thing is sort of a Rosetta Stone for equivalent notations, true Snellen fractions, magnification requirements and – voila! – visual acuity scores. Turns out visual acuity scores are no more than letter counts.

If you have a visual acuity score as required by the stem cell clinical trial, your Snellen fraction is worse than 20/320. In other words you see at 20 feet as well as people with good vision see at 320 feet or even further away. This is in the severe vision loss range.

My vision is probably in the moderately impaired range. Those are Snellen scores from 20/80 to 20/160 according to the chart. Bluntly put, I got in the APL-2 study partially because they are confident enough they won’t screw things up that they are willing to give the experimental treatment to people who still have fair vision.

The LumiThera treatment? Guess what all you folks with mild vision loss…that one will be for you! They are working with light therapy to reduce drusen size before there is significant vision loss. Yippee!

So, here we are, working together to share and advance knowledge. Severe loss, moderate loss and mild loss people all pitching in to contribute where they can. Sort of gives you a warm and fuzzy feeling; doesn’t it?

And by the way, guys? You rock!

Next: Bad News, Good News

Like Sorting at Hogwarts

Back in the retinologist’s office. How delightful. I seem to have done pretty well on all of the tests except one. I am back here for a re-take. Hope they grade on a curve!

Not sure what happened. I really thought I was doing great. OK, so I often think I am doing great, but all the signals I got were positive. I was even told I was most likely in. Now I am not so sure.

I had no idea this was all so involved! I was here for nearly four hours the last time I was here. I had all sorts of eye tests and even a few physical ones such as a blood test and a blood pressure test. It was rather grueling, especially since we worked through lunch.

This time I am supposed to be here for less than an hour. Just the same, I brought a drink. I am not used to going for four hours without any fluid intake.

I am supposed to come back in a week. I guess that I am coming back in a week. I guess that depends upon whether or not I pass this test today.

Anyway, the next time is supposed to be something like four hours. Think I will pack a lunch.

The next time I am supposed to be “randomized”. Basically that means I will be sorted and assigned to an experimental group. Sort of like sorting at Hogwarts, for you Harry Potter fans. Just minus the talking hat. Gee, maybe I will get into Gryffindor!

They are running two experimental groups and a control group. The one group is monthly injections of the medicine. The control group is their pretending to give the shot and the second experimental condition involves altering the shot with medicine and the “pretend” shot. That mean I have a 66% chance of getting the medicine at least every other month.

Not that I believe I could influence the growth of my lesions just by believing I am getting medicine, but I will not be told which group I am in for just that reason. What people believe can influence the dangedest things, including physical things. It is called the placebo effect.

Three days later…

Well, I am still not sure if I am in, but I do know what happened to the one test. It was technical difficulty, a machine glitch. Nice to know it was not me.

I am supposed to get word by the end of the week. That would be nice. However, I am not holding my breath.

If I have learned anything in these last few weeks, it is to expect the process to be more complicated than it initially seems like it should be. There are secondary, dependent variables being assessed, for example. There is also a big, huge bureaucracy behind the scenes calling the shots.

Anyway, should be interesting. Now all I have to do is get in…and stay in for three, long years.

Written April 23rd,2019

Next: Finally a Lab Rat

Cool Things

Greeting! I decided to stay home today. Too much to do. So instead of doing housework or work work I am working on a page.? Hey, makes sense to me!

I was doing a little web browsing and came upon the site for the “American Association of Ophthalmology. Protecting Sight. Empowering Lives”. Nice motto. Established 1896. Fairly old for ‘the colonies’.

I was looking through the sight site ? and discovered the pages from the annual meeting in New Orleans. There, in living color, was my doc! Carl Regillo was program co-director for the retina section. How about that?

Ever play Six Degrees of Kevin Bacon? It is a silly game based on the theory of six degrees of separation. The theory is anyone can get to anyone else in six moves or less through associations. I used to be able to get to the president in four moves. I was friends with the father of the secretary of the state department of agriculture. He knew the federal secretary of agriculture. The federal head knew the president. The president was my fourth jump. Done in four moves!

Anyway, started to think how many moves it would take to certain people through Regillo. He cuts it down considerably! But that is not my point…

My point is: they are doing some cool things in ophthalmology!

For example? Well, do you remember I said it would not be long before they are using gene therapy with AMD? Boy, was I behind the curve! Things in that field are happening now!

The AAO stuff was in abstract form and pretty scientific. Allow me to go to the popular press and get my info? If I sit down and try to analyze the other stuff, that is all I will get done today!

BrightFocus and WebRN both ran pages on gene therapy for macular degeneration. The BrightFocus article highlighted a gene therapy called Retinostat. Retinostat is for wet AMD. It sounds as if the inserted gene programs the cells in the eye to produce anti-VEGF. Sort of like refitting a factory to produce a different product.

Retinostat is nct01678872 at clinicaltrials.gov. What is listed is a phase 1 study (safety and tolerability) and they are recruiting by invitation only.

The second wet AMD gene therapy possibility mentioned in BrightFocus is AAV-sFLT. This is also supposed to block VEGF. This study is nct01024998. It is active but not recruiting. That is also phase 1. At the end of the first year, gene alterations from AAV-sFLT were still blocking the production of VEGF. Bottom line may be fewer or even no shots!

And, as for usual, wet AMD advances seem to happen first and our third potential gene therapy is also for ‘youse guys’. Specifically it is REGENXBIO’s RGX-314. The number is nct03066258. It is phase 1 – once again – safety and tolerability and absolutely no promises. They are recruiting. Santa Barbara, Baltimore, Boston, Philadelphia, Memphis and Houston.

So, yes. There is progress there in gene therapy for wet AMD, too. Gene therapy is in its infancy and some people object. It is up to you to decide for yourself if you believe manipulating the very code that makes up who we are is moral or are we playing God. Not my call. If you are alright with it, they could have it for you in a few years. Good luck!

Written January 28th, 2018

Continue reading “Cool Things”

Clinical Trial Design: Part 2

Page 2, almost done. Promise.

Types of Variables

Good experiments have independent and dependent variables. The independent variable is the treatment. The dependent variable is the result or what they are measuring.

Again, the idea is to keep as much as possible the same between our two or more groups. The groups are generally treatment(s) and control. Control groups get the sham ‘treatment’. The only things that ideally should be different among the groups are the independent variables, treatments.

In reading a study you can tell what your chances are of getting a treatment by checking how many different treatments they are looking at. For example, if there are three, different quantities of stem cells they are inserting and only one control group, you have a 75% chance of getting a treatment.

The Statistics

After the experiment is done, the researchers do statistical magic and find out if there was a real effect of the treatment. They want to see if what happened could have happened by chance. If there is little chance that it did happen by chance, they are that much closer to finding an effective treatment. At least in the studies I am interested in, people in the control group are offered the effective treatments when the experiments are done. They are not out of luck.

Remember, the medical research we may volunteer for has been done many times on laboratory animals. Unless you are very brave and sign up for a phase 1 clinical trial, other people have had the procedure before you. Real research is published in reputable journals. Ask where their initial findings were published. If you don’t get a decent answer, be very cautious. If you do get a journal reference and cannot interpret it, send it along. I don’t guarantee we will get it right, but we will give it the old, college try.

Size of the study

Also, in research there is such a thing as a cohort. A cohort is a group of subjects going through the same treatment pretty much at the same time. Phase 1 cohorts are small, maybe 7 or 8 people, but phase 2 cohorts may be a couple of dozen people. There are more people in the higher phases. If you are told you are the only one or one of just a few, be suspicious.

Those are some of the things that legitimate research have as well as a couple of extra tips on making sure you are looking at a legitimate study. The information is pretty dry but having access to it is better than falling for a bogus offer and being rendered blind. That is, after all, what we are all trying to avoid!

Just remember, caveat emptor. Check things out very well first. Continue reading “Clinical Trial Design: Part 2”

Clinical Trial Design: Part 1

The Hypothesis

All good experiments start with a hypothesis. A hypothesis is an educated guess about what should happen under a certain set of conditions. For example, “stem cells can grow in the eye and replace worn out RPEs”.

The way I was taught, this statement is then ‘turned around’ to be the negative. “Stem cells cannot grow and replace worn out RPEs”. This ‘turned around’ statement is called the null hypothesis. This is what will or will not be disproven with our experiment. The idea is to see if we can generate a result that will be significantly different from the starting point. The null hypothesis predicts no change. We want to see if we can affect a change that is big enough to matter. Good so far?

The Plan

After deciding what we want to figure out, we need a plan. Our plan is our experimental design. We want to design our experiment so we are reasonably sure there are no stray influences that may have caused the results.

 

The groups

If we are comparing treatments or treatment versus no treatment, we need to make sure our groups are as similar as possible. If we want to see if our new exercise program is better than another training program we really would (ethically) not want 20 year olds in one group and 80 year olds in another.

This is part of the reason good experiments on clinicaltrials.gov list exclusions which means reasons why a person couldn’t be in the trial. They are looking for similar subjects. Another reason for exclusions may be related to the treatments they are using and people’s sensitivities to them. You don’t want a subject who has an allergic reaction to your treatment!

The Sample

Once we have our sample (all possible examples or cases of something is called the population), we should be reasonably sure we have controlled for most of the important variables. Variables are factors that can affect the outcome of our study. However, there are other variables we have to control for in our experimental design.

The Treatments

One of these is the Hawthorne Effect. Anyone who has ever taken intro to psych or industrial/organizational should remember the Hawthorne Effect. In a plant they were trying to increase productivity. The problem became, no matter what they did, production improved! These people could have been working in the dark with the heat turned up to 90F but they were going great guns.

The researchers discovered just the fact that they were noticing the workers and trying to do something for them was enough to increase productivity. It did not matter that working conditions worsened. The workers felt noticed. They wanted to please the researchers.

Placebo effect happens when subjects believe the ‘treatment’ is effective even though it is not. They may show improvement as a result of their belief.

You will see attempted control for the Hawthorne and Placebo Effects in studies that list themselves as ‘double blind’ or ‘double mask’. They will perform fake (sham) procedures on people in the control so they feel noticed and loved, too.

Double blind? The double is because doctors and nurses treat people getting the actual treatment differently. They may not realize it but they may be more encouraging to those actually getting the treatment than they are towards the people who are the controls. When a study is double blind neither the patients nor the people caring for them actually know.

That is my 500+ words for this one. One or two more pages and I should be done. Hang in there!

For more information, click here for Designing Experiments Using the Scientific Method from dummies.com.

Continue reading “Clinical Trial Design: Part 1”

Highlight: Dry Macular Degeneration Clinical Trials 1/7/2017

There is no current treatment for dry AMD.  There IS encouraging research and for those of us who subscribe to the newsletter from WebRN-MacularDegeneration, we just got a link to a page that discusses ‘a sampling’ of the studies including for those with geographic atrophy which is one of the advanced forms of AMD.   Several of the studies are looking for participants.

Click here to go to Dry Macular Degeneration Clinical Trials.  Number 3 is the study that Sue is waiting to participate in.

WebRN-MacularDegeneration is a great website & I recommend that you subscribe to the newsletter.

News: August 23-24, 2016

Super Lab Rat

So now I am reasonably sure I have a shot at becoming a test subject. Never really believed one of my greatest ambitions in life was going to be to become a lab rat. However, I can assure you I had ambitions to be the best damn lab rat Wills Eye has ever seen. My visual gains will be extraordinary! I will become spokes-rat for the program and travel around the area doing the ‘rubber chicken’ circuit. I will be brilliant. (Did I happen to mention I have no problems generally with my self-esteem? Perhaps…can you spell megalomania?) I even designed my t-shirt. It includes a drawing of a cute little mascot that will, of course, represent the hospital for decades to come.

I will be the best damn lab rat Wills eye has ever seen! I’ll become spokes-rat for the program and travel around the area doing the ‘rubber chicken’ circuit.

I did continue my research. I wanted to know what exactly I was getting into. I’m not one for invasive procedures or even for a lot of ‘doctoring.’ However, assuring vision for myself in the future tended to trump all other considerations.

Although Regillo tended to gloss over some of the more gory and unpleasant details, I wanted to know. My source was the 2015 Lancet article on the Phase 1 experiment.

Let me go off on a tangent here for a moment. Until I got into this, I had no clue what happens in clinical trials. Short tutorial if I may: clinical trials are made up of four phases. The first phase is a safety and tolerability phase. Essentially, the researchers are looking to make sure that nothing serious goes wrong. They want to make sure that no one has an allergic reaction or grows stray body parts where they should not be growing.

In Phase 1 they want to make sure no one has an allergic reaction or grows stray body arts where they should not be growing.

After Phase 1, the efficacy experiment starts. They want to see how their treatment actually works. Does it do what they claim it will do? They also start messing around with different independent variables to see what works best. In the study I am trying to get into, for example, they are comparing different immunosuppressant drugs to see which one works best. In other Phase 2 experiments they compare slightly different operation procedures or any more of the dozen of different treatment variables. All Phase 1 studies use only a very small number of people, Phase 2 studies use many more.

In Phase 2 they want to see how their treatment actually works.

As I understand it, Phase 3 studies are essentially larger variations on Phase 2 studies. Techniques and procedures are refined and the subject pool is made up of hundreds or even thousands of people.

In Phase 3 they perfect the techniques and procedures on more people.

Phase 4 is sort of like an off-Broadway show or traveling company. Instead of just being administered by people at the experimental sites, the procedures are now made available to other professionals to try. Reports are made back to the original team. By this time, the subjects can number in the thousands. Once a procedure gets through Phase 4, it is ready for prime time. If good enough, it can become standard procedure around the globe.

In Phase 4 they make their procedures available to other professionals to try at other locations.

Written February 2016. Updated 2018.

Continue reading “Super Lab Rat”

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