Targeting HD Early:
How You Can Help through the FuRST-pHD Study
If we are serious about clinical trials to address pre-manifest and very early Huntington's disease (pre-HD), we must begin by completing the FuRST-pHD study. A recent study of PREDICT-HD participants indicated just how vital this work is. You can help us reach the goal for completion of this important study by December,2010.
What is FuRST-pHD? CHDI Foundation is sponsoring this study: -- the Functional Rating Scale Taskforce for pre-Huntington's Disease (FuRST-pHD) -- to develop a functional rating scale more sensitive to change in pre-HD than the standard UHDRS scale.
Why do FuRST-pHD? The FDA will approve a new drug for pre-HD only if improvement in function can be shown. But the present UHDRS functional scale, or TFC, was developed as a clinical scale to measure functional change for those with manifest HD., and not designed for use in pre-HD (1). In a recent scientific article, Doctors Jane Paulsen, Dan van Kammen and colleagues have shown the need for a new functional scale for pre-HD .
The PREDICT-HD Background: To assess how well the standard TFC scale can measure change in pre-HD, PREDICT-HD researchers followed participants for an average of about 3 years. The researchers studied how effectively the TFC measured change in pre-HD. TFC consists of a 13-point scale with higher numbers reflecting higher function, and lower numbers loss of function as the disease progresses. They found that almost 90% of participants had maximal TFC scores (13 points), In other words, TFC did not sensitively separate those predicted to be near to, from those farther from disease onset. And importantly, the researchers found that the yearly rate of change in TFC - which is the measure now used in HD clinical trials -- was very slow, averaging only 0.06 TFC points per year. This is a much slower rate of change than the average yearly decline of 0.72 points in manifest HD.
In practical terms this means that if TFC were used as a functional outcome in clinical trials for pre-HD, these trials would require thousands of participants -at least 10 times those needed for trials of symptomatic individuals. So more than 6000 pre-HD individuals would be needed to conduct a CoQ-10 or creatine trial that would be similar to 2-CARE (CoQ-10) or CREST-E (creatine) clinical trials now underway for those with more symptomatic HD.
These numbers should tell us just how vital it is to develop a new functional scale for pre-HD.
Rationale for FuRST-pHD: In the PREDICT-HD study investigators also sought to define problems that most frequently limiting function in the pre-HD group. Problems with work were the most commonly reported early functional impairment, indicating that this measure could more accurately identify time to predicted onset of disease.,
The researchers performed a similar study on behavior symptoms in HD. They found that certain components of depression were better measures of change in pre-HD than those in the standard UHDRS depression scale. The latter combines such symptoms as irritability, low mood, lack of interest in enjoyable activities, and fatigue. Rresearchers also showed that measures of energy levels were more sensitive to change and more related to predicted time of onset of disease than mood symptoms. Similarly, motor and cognitive subscales were used to identify the individual factors more sensitive to change.
FuRST-pHD Study Design: This study is based on sequential interviews. Early ones take between an hour or two and include multiple questions relating to work and home functioning, cognitive or thinking issues, motor symptoms ranging from difficulty in reading (due to impairments in eye movement) to difficulty with balance, and behavioral and emotional symptoms that are categorized into many different components. The answers allow researchers to identify the more problematic symptoms, and further refine the next round of interviews.
The ultimate goal is to develop an efficient list of "best questions" to optimally capture the changes and functional difficulties that occur in pre-HD. The goal is to have interview testing done by the end of 2010.
A huge THANK-YOU to PREDICT-HD participants and to those who have already participated in FuRST-pHD interviews. Now we need your help:
- If you or someone else you know are pre-HD or within 2 years of motor diagnosis by your Doctor, you are eligible.
- If a center near you conducts the PREDICT-HD study, call and find out if they are also participating in FuRST-pHD. If so, volunteer!
- If you are not near a FuRST-pHD study center, you may still be able to participate. CHDI Foundation is working to make it convenient for you. If you can form a small group of volunteers in your geographic area, I will come to a location near to you to conduct the interviews-- at a time convenient for your work schedules.
- If you are a support group leader - organize your group and contact me at firstname.lastname@example.org.
Working together we can begin targeting HD early in the disease process through your essential participation in FuRST-pHD.
 Marder K, Zhao H, Myers RH, Cudkowicz M, Kayson E, Kieburtz K, Orme C, Paulsen J, Penney JB Jr, Siemers E, Shoulson I. Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology. 2000 Jan 25;54(2):452-8. Erratum in: Neurology 2000 Apr 25;54(8):1712.
 Paulsen JS, Wang C, Duff K, Barker R, Nance M, Beglinger L, Moser D, Williams JK, Simpson S, Langbehn D, van Kammen DP; the PREDICT‐HD Investigators of the Huntington Study Group. Challenges assessing clinical endpoints in early Huntington disease. Mov Disord. 2010 Jul 9.