Do You Need a “Partner in Crime”?

butchnsundance

The topic today is Trial Partners. Sometimes we researchers refer to them as Study Partners or Informants, the latter of which can cast a negative connotation onto the role.

Before this decade, clinical drug trials for Alzheimer’s disease that had proceeded to Phase 2 recruited patients who had clearly developed symptoms of this type of dementia. The same held true for trials for patients with the other types of dementia: vascular dementia, frontotemporal dementia, dementia with Lewy bodies. By definition then, these participants were ethically vulnerable to proscription into trials. If you can’t remember what the study entails, are you qualified to consent to participation? If you lack the ability to weigh the consequences of your decisions based on other cognitive deficits, are you really able to understand that your participation in the study is voluntary? Could you get yourself out of the study if it proved unsafe or inconvenient or even painful for you?

To help protect participants with cognitive impairment severe enough to qualify as dementia, researchers enlist a trial partner for each vulnerable participant. Not only could the trial partner vouch that the researcher had not coerced the patient into participating, but that partner was likely a more reliable historian about possible side effects or disease progression over the course of the study. Recall that some types of dementia reduce the patient’s ability to perceive his/her own deficits or to remember them long enough to report at scheduled visits to the trial site.

We’re now at an exciting milestone for Alzheimer’s clinical trials. We have begun to test medications that would stop the disease process before significant losses occur. The recruitment of participants to these studies therefore does NOT include those who won’t remember the study drug dose instructions or who can’t sign informed consent themselves. Do these independently functioning, non-demented participants need to have trial partners?

It may depend on the nature of the clinical trial you are considering. If you are fully independent in daily life, maybe a bit forgetful but doing great with a smartphone to keep you on track with reminders and appointment alerts, you could probably handle signing informed consent and participating in a brief (1 year or less) study. The study would end before you could not make notes and keep appointments by yourself. But some of the new trials are designed to go beyond a single year. One we’ll soon launch in North America will last 4.5 years. Given that recruitment is geared toward elderly people at a higher risk for Alzheimer’s disease than their age-peers, chances are good that cognition will change over that period of time. And we will need a person who is objective and qualified by the participant to give us a sense of that change over time.

Some things to keep in mind when you choose a trial partner:

  • Being a trial partner means accompanying the participant to some or all visits. If your potential trial partner has a busy schedule or health considerations that make traveling with you difficult, it’s better to pick someone else. The trial partner does not have to live in your home with you.
  • It’s not an automatic assumption that your spouse/partner will make the best trial bonniepartner. If you tend to disagree with that person’s impression of you or if your relationship is the type that doesn’t tolerate taking instruction, you might want to choose someone else. Trial partners often serve as another pair of ears for the study instructions, and therefore they may act as “deputies” to help make sure the study protocol is followed.
  • If you will be counting on the trial partner to help you stay organized (what pill pack this week? When do we go back in for a brain scan? Which location do we go to this time?), pick someone who you think can fulfill that assignment. The study team will do their best to send reminders, but a disorganized trial partner can derail your completion of study-related tasks.
  • Who’s your back-up? We have seen some trial partners “fall by the wayside” during a study. Some of this is due to other life matters having to take priority or unexpected health issues or even death. Most of us will be happy to sign you on with notes about who might act as your second trial partner, even if this manifests as a short-term, transient occurrence.
  • Not all studies will allow two life partners to be each other’s trial partners. If one develops dementia despite participation in the study, that brings us back to “Who’s your back-up?” above. Research teams may benefit when you reach out to the rest of your social circle – getting others outside of your household involved helps spread the word and speed up recruitment. Speeding up recruitment speeds up the time we’re all waiting to reveal whether the study drug worked the way we wanted it to.

New Brief Study – Older Volunteers Needed

mindspa-2

We are seeking 5 individuals over the age of 65 to test the tolerability of a light therapy non-medical device worn as sunglasses for 20 minutes daily. Trial length: 5 consecutive days.

To volunteer or for more information, please email Dr. Tiffany Chow, tchow@usc.edu or 858-964-0462

Study conducted by Tiffany Chow, MD (USC Dept. of Clinical Neurology)

USC IRB HS-16-00440
Date of Preparation: 6/29/2016

Poetry Corner

One Afternoon at Teatime

Marilyn Hammick

Arthur stops close to where we sit waiting
for the person you call the activities lady
to serve us drinks and biscuits.
He moves his wheelchair with slippered feet,
so we become another group.
You introduce me, This is my sister,
I nod to Arthur and watch his mouth form words
that seem reluctant to reach me, hang
in the air unsteady, diminished.

He continues to speak, I continue to nod,
I think he’s asking about my name,
you seem to understand, or do you guess?
I’m trying to work out if there’s a knack
I’ve yet to grasp, a way to hear
the hush and lisp of his voice, because
all the time you’ve been here, where
you don’t want to be, after all these months
Arthur is the first person you’ve introduced me to.

We choose our biscuits, I drink tea, you have coffee
Arthur has half milk, half coffee and continues to speak.
I think he’s talking about his family, two daughters, a son,
I’m unsure so I ask is he watching the rugby?
No, his game is football and there’s something
about a golden goal. I say what position did you play
and hear, clearly, outside left.
Something rights itself inside me.

About the poet:

Marilyn Hammick retired in 2013 from her international consultancy in medical and healthcare professional education, specializing in evidence-informed education, systematic reviews and interprofessional education. Previously she was in clinical practice as a therapeutic radiographer. She writes (and reads) when traveling, during still moments at home in England and France, and when recalling her childhood in New Zealand and years living in Iran. Her poems have appeared in Obsessed With Pipework, Prole, The Interpreter’s House, The Linnet’s Wings, The Journal, I am not a silent poet and Nutshells and Nuggets. She was named a “Spotlights poet” in Paragram’s 2015 pamphlet competition.

About the poem:

“My sixty-year-old brother lives, somewhat reluctantly, in a residential-care home. He is now safe, well fed and on the correct medication, and has help with personal care. But he feels that the independence he highly valued as a person with a disability has been taken away from him. His brain damage means that he’s resistant to explanations of why he is living in the right place for him at this time of his life. Most days he sits alone or remains in his room. This poem came from the joy and relief I felt after visiting him as described. Poetry gave me the opportunity to voice my emotions about a small, positive change in his attitude to his new home, and the importance of that to me.”

Poetry editors of Pulse

 

Not Quite Confirmation of Alzheimer’s Protective “Do’s”

3d-audience

  • Participating in arts and crafts (not just shopping for them)
  • Using a computer
  • Playing games (this is where the Chinese say, “Aha! Mah Jong!”)
  • Social activities (example given in this article was moviegoing)

All correlated with reduced incidence of Alzheimer’s disease among people over age 70 yrs who already have some memory deficit. THIS MAY MEAN that people engaging in these activities are doing so BECAUSE they are not on the way to Alzheimer’s, as opposed to the activities themselves being preventive, but it does support what activities  we’ve been claiming to boost cognitive reserve.

Of interest, participants were said to partake of those activities even if they only engaged on a weekly basis, which tells me it may not have to change your life by much to commit to this program.

I’m disappointed that Reading, one of my personal favorites, did NOT come out with a statistically significant correlation. It has shown some effect when following people starting from a time BEFORE memory impairment, but did not rank with the others above.

for more on this study, click here

 

 

Ome-oma

Our understanding of how genes eventually relate to brain disorders continues to evolve, and along with it, the terminology:

Genome: it started here. Technology at first let us have brief peeks at “neighborhoods” of genes. As we developed methods for looking at neighborhoods with relation to each other and their relative production rates, we became able to consider

Proteome (integrity of finished protein product’s structure) and Transcriptome (how RNA plays its middleman role) make sense as factors in how much impact the genome could have on an individual’s health. But wait, there’s more, lots more:

Metabolome: the flip side of that productivity coin: if the protein made from the genetic instruction manual is being broken down in an abnormal way, you might have too little or too much of the protein, even if your body knows how to make it.

Connectome: specific to neuroscience. How your brain regions are physically connected to one another (which includes what structure you were born with and what structure you may acquire from stroke or head injury or infection) plays a role in how well or not well the proteins function in that brain.

Epigenome: I used to conflate this with the next section. This refers to the methylation process, which is a way to flip a railroad track signal to enhance or inhibit the transcriptome.

Interactome: the interactions  of genes with each other (2 wrongs can make a right or there can be some wonderful synergies)

Exposome: a way to throw environmental exposure, life changes, accidents into one category.

For more, see Dr. Andy Saykin (and ADNI Genetics Core)’s review.

The title for this post refers to how we medically name tumors (rapid unintentional growths) after the cell type + oma, e.g., meningioma.

Learning from Biotrial

Some of you may be hearing about the 6 participants in a French study of a new drug to act within the brain. Our institute is not involved with that study, but the developments of serious brain injuries from a drug trial that had actually been going along without problems for the last half of 2015 have certainly served
to let me run through what processes we have in place for similar emergencies in our studies. 
This type of thing, where 6 participants are hospitalized, is more likely to happen in Phase I trials where the drug’s safety in humans is first being tested. Our portfolio of trials are all at least in the Phase II stage, but to have adverse effects in the older target populations with dementia may be significant (become serious) because of their age and other coincident health status. 

I read through a major investigational review of a similar incident from the ’90s and was relieved that there can be a clear protocol for safety after the unexpected has struck: both internal and external reviews of the drug risk and the participants’ conditions start immediately, and any prior history of similar reactions during trials of the same drug are brought forward for pattern recognition. Ethics, safety, and protocol reviews go on simultaneously to right what can be remedied and protect any participants who are still in the study but potentially at risk. 

One newspaper article about the current dilemma quoted an external researcher as warning that volunteer participants for Phase I studies might not have the education to understand what they’re signing on for but the money to be made is compelling. From another article, it doesn’t seem like an unusual sum was given for the study in question. Time will tell what we can do better in future. I’m hoping we’ll find ways to reassure our recruits that we are watchdogging for safety from the point of designing the study, right on through.

Epilogue to the story? I couldn’t find anything July 10, 2016, 6 months after the Bial cannabinoid incident about how the investigational drug might have been related to the brain hemorrhages, but Biotrial issued this press release in May exonerating them from any trial misconduct.

Confirmation: Estrogen Supplementation is NOT a Treatment for Alzheimer’s Disease

older-womanFormer USC colleague, Dr. Vic Henderson, and his group at Stanford published results of their randomized, placebo-controlled clinical trial of a selective estrogen receptor modulator for those women who already have mild-moderate Alzheimer’s disease.

In a nutshell, there were no differences in the progression of the illness after a year, whether participants were on placebo or raloxifene. This confirms the ongoing consensus that estrogen may play more of a role in cognitive health based on what happens earlier in life BEFORE memory problems of aging take place.

The article: Henderson V et al. Raloxifene for women with Alzheimer disease. Neurology 2015; 85: 1937-1944.