Study concluding large-scale data collection

By Sean Thompson

PREDICT-HD Public Relations Coordinator


After starting out as a Huntington disease researcher and clinician in the 1990s, Dr. Jane Paulsen began to notice a common theme in discussions with HD patients and families.


Jane Paulsen med

Jane Paulsen
PREDICT-HD Principal Investigator

"They would tell me that before their loved one was diagnosed with manifest HD, they were noticing changes in the way he or she behaved," said Paulsen. "Or maybe their once-punctual family member was now frequently late for appointments. It's the families that really brought these early changes to the forefront and drove me to start the PREDICT-HD study."


The study that set out to identify those earliest changes and signs of HD so the course of the disease could be better understood and treatments could be targeted to keep people healthy longer was first funded by the National Institutes of Health (NIH) in 2001. Thousands of participants, 90-plus medical journal articles and 13 years later, PREDICT-HD, as it is currently constituted, is concluding.


Thirteen years of sustaining support

Over the life of the study, hundreds to thousands of research visits were conducted each year at as many as 32 worldwide study sites. This immense data collection effort has been funded by multiyear grants from the NIH as well as grants from the private HD research-funding CHDI, Inc. The term of the final NIH grant to fund the multisite, annual visit data collection ends on Aug. 31.


Paulsen, PREDICT-HD's principal investigator, said she is very pleased with the support PREDICT-HD has received from the NIH over the years.


"Studies come and go all the time, so in that respect, we've been very fortunate," Paulsen said. "To have had the support of the NIH, CHDI and of our participants and collaborators for 13 years is really quite extraordinary."


"There's always more we want to learn about the earliest signs of HD and we intend to do so going forward. But if you had told me in the beginning we would've conducted a multisite study like this for 13 years, I would've been thrilled at that opportunity, as I am at the end of the multisite study this year."


A collaboration of participants, families and researchers

Dating back to those early conversations Paulsen had with HD family members, PREDICT-HD has focused on its participants and their families, the people who make it what is. If you thumb through the pages of the first PREDICT-HD participant newsletter, it is evident there.


"Partnership among HD families and scientists has never been so critical," the newsletter reads. "Today's goals toward an improvement for HD require collaboration among scientists and family members."


Though she has always believed in the HD community and their willingness to participate in research, Paulsen says having 500 people (the original PREDICT-HD participation goal) give up a day or two of work or travel many miles to take part in research seemed like a daunting prospect at times. However, participants from all walks of life signed up to be a part of the new study, and the original goal was tripled, with more than 1,500 participants over the life of the study.


"Our participants give their time, their energy, their effort and concentration, and provide biological samples like cerebral spinal fluid," Paulsen said. "Without that aspect of selfless participation, we could assemble the most brilliant HD researchers in the world, and we wouldn't get anywhere toward our goal of making a difference in the lives of people with HD. It's really the participants that have taken this study to great heights."


Stephanie and Kerry
 (from L to R) Participants Stephanie Bernander and Kerry Eldred were at the 2013 HDSA National Convention PREDICT-HD booth to talk about participating.

Furthermore, participants have contributed by way of providing feedback that has helped the study evolve. Study tasks have been added or removed based on participants' comments and suggestions. In 2011, a research participant came to study staff with the idea of making a video showing what a PREDICT-HD research visit is like. That participant later starred in the video that was filmed and posted on YouTube as a way to take the mystery out of participating in a study like PREDICT-HD. And at the 2013 Huntington's Disease Society of America National Convention, study participants were at the PREDICT-HD booth to tell people what participating in the study was like.


And whenever participants have been asked to take part in a new aspect of the study like cerebral spinal fluid collection, Paulsen says they have been very willing to do whatever it takes to contribute further to HD research.


"We are so appreciative of people's willingness to take part in all the different things we ask of them as part of the study," Paulsen said. "It's heartening to us as researchers when people want to do whatever they can to contribute to the study."


According to study surveys, about 95 percent of PREDICT-HD participants say they participate in part to "help improve the outlook for the next generations of my family and all families with HD by contributing to research aimed toward treatments and a cure," and 78 percent say they feel more hopeful about HD when they are able to do something positive about it, like participating in research. PREDICT-HD participant and HD advocate Lauren Holder of North Carolina says she sees her participation as a way to do something and get involved.


"You're doing this to help the Huntington disease community and help research," she said. "I feel like I'm actually contributing whenever I participate in research."


Impactful findings

Imaging figure
 This image shows changes in brain volume in various parts of the brain, from a PREDICT-HD article published by Jane Paulsen and coauthors in Brain Research Bulletin in 2010.

Much more is known about the course of the disease in general and the prediagnosed "prodromal" phase of the disease as a result of PREDICT-HD findings. Numerous early signs of HD in the areas of brain imaging, cognition (thinking ability), psychiatric symptoms and movement symptoms have been identified, some occurring decades before a traditional motor diagnosis would be expected to occur. These early signs could also be outcome measures for therapeutic trials aimed at slowing or preventing HD, according to a review article about PREDICT-HD by Dr. Edward J. Wild and Dr. Sarah J. Tabrizi in The Lancet Neurology in 2006.


Other PREDICT-HD findings published in medical journal articles have shown that clinical trials in this prodromal phase of HD are feasible, which is something Paulsen says many families have been hoping to hear, to eventually provide treatment to allow people to remain healthy as long as possible.


The traditional motor diagnosis of HD is not fully effective, other findings show, and a multidimensional diagnosis could lead to a better definition of various stages of prodromal HD.


PREDICT-HD findings touch on a variety of topics beyond identifying early disease signs. Results indicate cognitive reserve may delay the onset of changes in the brain caused by HD, and a separate report shows couples used positive coping strategies that they found to be effective in dealing and living with HD like acceptance and planning.


In total, over 90 medical journal articles have been published reporting findings from PREDICT-HD. But you won't only find study results on journal pages. Findings have helped inform the Huntington's Disease Society of America in its advocacy efforts to pass legislation to update outdated federal Social Security Administration definitions of HD and end waiting periods for deserved disability and Medicare benefits.


An ongoing effort

 Though large-scale data collection through repeated annual testing is concluding, PREDICT-HD research continues in various forms.

Though the multisite, large-scale data collection configuration of PREDICT-HD is concluding, several ancillary studies funded recently by the NIH are ongoing and will require smaller-scale data collection. Paulsen and her PREDICT-HD colleagues are also pursuing funding for additional HD research projects that would involve the HD community as participants, and more will likely be formulated as researchers continue to analyze the data collected in PREDICT-HD.


"With PREDICT-HD as it's currently constituted concluding, our HD research continues," Paulsen said. "With each new finding we report on, we're moving closer to supporting the development of clinical trials in this early pre-motor diagnosis stage."


As they have for the past 13 years, PREDICT-HD participants will continue to be a big part of that process. Whether they continue participating in current or future PREDICT-HD related studies, roll their participation into the new worldwide Enroll-HD study or whether their previously collected data continues to inform HD research around the world, Paulsen says their contributions have been (and will continue to be) significant and appreciated.


"I am very proud to call each of our participants partners in this effort to make a difference in the lives of those affected by HD," Paulsen said. "We look forward to ongoing collaboration between researchers, participants and families to continue working toward this goal."