HOPES team members Adam Hepworth and Amy Frohnmayer visited the UC Davis Center of Excellence team on August 2, 2007. The visit took place at the Veteran Affairs (VA) Hospital in Rancho Cordova, a facility which the Center uses for running clinical trials. During the visit the HOPES members had the opportunity to see exactly what takes place during a clinical visit for a participant enrolled in the COHORT trial. HOPES would like to offer thanks to all of the clinic staff who made the visit a positive experience with a special thank you to Teresa Tempkin for offering so much of her time and expertise.
Left to Right: Amy Frohnmayer, Teresa Tempkin, Adam Hepworth
Although the UC Davis Center of Excellence (COE) main office is located at the Davis Medical Center in Sacramento, our visit took place at the VA Hospital in Rancho Cordova. On the fourth floor of the main hospital building, an entire wing is devoted to clinical trials run by UC Davis doctors. The UC Davis COE had reserved space on this wing to run the COHORT clinical trial.
Tempkin explained that access to these clinical research facilities was crucial for successfully running clinical trials. At the VA Hospital, she has access to space and equipment unavailable at the Davis Medical Center. Without these resources, it would not be possible for the UC Davis COE to participate in clinical trials like COHORT.
COHORT is an acronym for Cooperative Huntington’s Observational Research Trial. It is currently the largest Huntington Study Group HD clinical trial and it takes place at 40 sites in North America and Australia. It is a long term observational study with no official end date. The goal of the study is to collect a huge database of information from subjects diagnosed with HD and make that information available to researchers around the world. To that end, trial enrollees commit to annual study visits for as long as they are willing and able. The study’s control group consists of adults who are part of an HD family. This particular study does not enroll individuals who are at risk of HD but do not know their gene status. The UC Davis COE entered the trial in January of 2007 and has already enrolled over 30 participants. For more information about COHORT click here.
Behind the Scenes of a COHORT Visit^
During our visit, we were fortunate enough to observe first hand most of what happens during an annual COHORT visit. In addition to a standard physical exam, the participant undergoes a few short cognitive and neurological assessments. A variety of questionnaires are also administered to the participant. These help assess the participant’s emotional and behavioral status and help to gauge the affect of disease progression on daily living and basic skills. The participant gives a detailed medical history and reports on any medications he or she currently takes. And finally, the visit includes a blood draw. With participant consent, the blood samples collected in COHORT are placed in a research facility and made available to HD researchers around the world. This is one unique aspect of the study that offers an amazing opportunity for HD researchers. Because all of the information collected during a participant’s annual visit is matched by code (all personal identification information is kept strictly confidential) to his or her blood sample, researchers using the samples can also have the benefit of knowing a huge variety of information about the status and progression of HD in the individual to whom the sample belongs. This additional body of information linked to every blood sample allows for much more sophisticated research and analysis.
Some of the procedures during the visit are fairly generic and could easily take place in any clinical research trial, while others are tailored specifically to HD participants. For instance, one of the cognitive tests administered was a short mental exam. One part of this test includes questions designed to measure a subject’s orientation in time and space, ability to maintain focus and attention, and basic communication skills. Although these are all important cognitive abilities, they are not usually the functions impaired by HD, which tends to negatively affect executive function. A later cognitive test looked specifically at executive function through tests of concentration and multitasking ability. That test tends to be more sensitive to cognitive changes in an HD patient.
The neurological examinations also include both more general tests and specific tests best suited for an HD population. Although it is common to think of chorea as the definitive neurological sign of HD, the COHORT neurological exam looks for many other HD-specific symptoms. Tempkin explained that although chorea is one of the most visually dramatic signs of HD, it is not usually the most debilitating aspect of the disease. Problems with balance and fine motor coordination are more likely to lead to serious complications through injuries like falls. Chorea is also extremely variable, and progresses at a different rate in different patients. This makes it especially important to test a variety of motor changes. The COHORT exam includes tests for characteristically abnormal eye movements, motor impersistence, speech changes, muscle stiffness or tightness, and balance impairment.
Administering the questionnaires about emotion and behavior may be one of the more difficult parts of the evaluation. The information from these questionnaires comes through the filter of the subject’s own perceptions. Frequently, the goal is to take the subject’s answers and turn them into numeric values along some scale, thus quantifying the measurement. However, assigning values objectively to subject responses can be difficult and some of the responsibility ultimately rests with the judgment of the investigator asking the questions and recording the results. In an effort to make the process as scientifically objective as possible, numeric values along the scales are defined very specifically. Investigators must constantly struggle to ensure that results from these questionnaires are consistent across subjects and across testing sites.
Tempkin emphasized that careful consideration of participant rights is an integral part of running a study like COHORT. No potential participant is ever pressured into entering the study or enters without the most comprehensive knowledge of what the study entails. Before enrolling in the study, every potential participant must sign a consent form. The seventeen page long document can seem a little intimidating, but every effort is made to ensure that the potential participant reads and understands the entire form.
Tempkin explained that when the patient first expresses interest in participating, the form is mailed to his or her home address. This ensures that there is time to read over and think about the form in a no-pressure environment. If the potential participant still wants to enroll in the study, he or she will come in for the first visit. At this point, Tempkin will verbally review the consent form with the potential participant, making sure that there are no misunderstandings. The participant will only be enrolled once Tempkin satisfies herself that he or she fully understands and agrees to all of the conditions.
Consent forms are a key part of protecting participant rights in clinical trials. There are some aspects of the consent form that remain consistent across all UC Davis studies. For instance, the form starts out with the Experimental Subject’s Bill of Rights, which states explicitly many of the participant’s most important rights. For instance, every subject is entitled to know what the study is trying to discover, what procedures will happen to him or her during the course of the study, and what the risks and benefits of the study will be. Additionally, the bill of rights guarantees that the subject can stop participating at any time and that failure to participate will not impact future medical care.
The seventeen page length of this particular consent form is due largely to the complexity of the COHORT trial. Different aspects of the trial, such as the medical history and the tissue sampling, must be consented to separately from the trial as a whole. This ensures that participants are fully aware of everything to which they are consenting and grants more participant flexibility. If a subject wants to participate in the trial, but doesn’t want to share his or her medical history, this is possible. Tempkin mentioned, however, that patients in the HD community tend to want to participate as fully as possible in the trials, because they know the huge importance and potential benefits of research studies like COHORT.
More about Clinical Trials in the HD World and the Davis Center of Excellence^
Although our visit focused on the COHORT trial, the Davis COE is currently involved with several other HD clinical research trials. The Predict HD trial enrolls subjects who are gene positive for HD but have not yet developed symptoms. One defining feature of this trial is very lengthy neuropsychological testing administered by a trained physician as well as volumetric brain scanning. The goal is to search prospectively for early neuropsychological changes that occur before any motor changes.
Another study in which the Davis COE participates is PHAROS. This study enrolls subjects who are at risk for HD but have never been tested. The study is generally looking for precursors to HD phenotype expression and includes a heightened emphasis on mood evaluation.
For more about these studies, as well as other currently active HD trials, visit the Huntington Study Group here.
The UC Davis Center of Excellence typically conducts clinical research trials like COHORT and the ones described above once or twice a week at the VA Hospital in Rancho Cordova. The exact amount of time spent at the VA Hospital depends on how many trials are ongoing. During the rest of the week, the center is active in Sacramento at the UC Davis Medical Center, where they run an HD clinic and a Parkinson’s clinic.
The Collaborative Nature of HD Research^
During our visit, one point that came up again and again was the collaborative nature of HD research. From scientists conducting basic research, to doctors running clinical trials, the HD community is engaged in a cooperative venture. Information is shared freely between researchers and frequent communication allows for a coordinated research effort. This is a unique atmosphere in the world of academic research and it can be partly attributed to the strong, dedicated presence of the HD community. Researchers understand the stakes in the battle against HD and realize that the importance of their work demands the best possible effort. Cooperation is a key part of that effort.