More questions from the ADAGIO results

The recent publication of the ADAGIO trial raises numerous questions for the community to consider. Many of these have been outlined by Dr. Kieburtz in his discussion with MJFF and Dr. Fiske on PD Online. Two others come to mind.

First, after a 20 year wait, this is a second try at assessing the possible disease modifying or neuroprotective effects of propargylamine agents in Parkinson’s disease. When selegiline was assessed in the late 1980’s, the clinically minimal symptomatic benefit observed confounded assessment of a disease modifying effect and sparked debate (Parkinson Study Group 1989; Tetrud & Langston 1989; Landau 1990).  Arguably, a similar conundrum presents today, at least in interpreting the effects of the 2 mg dose on the UPDRS-derived slope outcome.  Is rasagiline truly disease modifying? Is the delayed start design, like other designs based on clinically-derived outcomes, ambiguous when the drug has symptomatic benefit?  A biomarker of disease progression would help to resolve this. 

A second look at the utility of the delayed start design in early PD will soon be available from a MJFF-funded study. Under the leadership of Piu B Chan, MD, PhD, of Xuan Wu Hospital and Capital University Medical Center in Beijing, China, the Chinese Parkinson Study Group has recently completed a test of the hypothesis that green tea polyphenols (GTP) slow progression in early Parkinson’s disease.  We carried out a multi-center, double-blind, randomized, placebo‑controlled, delayed start study in 32 Chinese Parkinson Study Group sites. Four hundred and ten untreated PD patients with disease duration < 5 years and Hoehn & Yahr Stage < 3 who were not heavy tea drinkers were randomized to one of three doses of  GTP  (0.4, 0.8 or 1.2 grams daily given in 2 equal oral doses) or matching placebo. After 6 months, placebo was switched to 1.2 grams daily of GTP. All patients have completed 12 months of treatment.  Results of this trial are now being analyzed.

Whether rasagiline is neuroprotective or simply an efficacious symptomatic intervention in early PD,  the benign safety profile suggests that  rasagiline may be useful in those wishing to delay side effects due to l-dopa or agonist treatment.  In this situation, the question of comparative efficacy is also relevant. Are there advantages to rasagiline, compared to selegiline?