Effects of Tocopherol and Deprenyl on the Progression of Disability in Early Parkinson's Disease

Abstract

Deprenyl (10 mg per day) but not tocopherol (2000 IU per day) delays the onset of disability associated with early, otherwise untreated Parkinson's disease. The action of deprenyl that accounts for its beneficial effects remains unclear.

A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY‐PD III)

“…These outcomes include time to initiation of ST, time to the development of motor complications, use of ST and nonmotor disability. Time to initiation of ST has been a primary outcome in several completed studies that examined the efficacy of putative disease‐modifying interventions 5, 29. Although it has been criticized for the subjective nature of the measure and being impacted by the change in the treatment algorithms that overall lead to the earlier initiation of ST, nevertheless it can be considered a surrogate measure of the disease progression and allows us to compare our findings with previous trials.…”

“…We also considered a prolonged wash out at the end of study or at the time of initiation of ST to reassess for the evidence of symptomatic benefit, but there are strong arguments against such design, including lack of obvious symptomatic effect of isradipine in our Phase II STEADY‐PD2 study and participant burden. In addition, there is no consensus regarding the necessary duration of the washout that would be required for isradipine 5, 28. Therefore, our design represents the most rational approach to study the efficacy of isradipine on disability in PD.…”

“…Key secondary outcomes of clinical importance have been identified and include: (1) Time to initiation of ST has been used as a primary outcome measure in several previous studies of putative disease‐modifying agents5, 29 and reflects progression early in disease not obscured by symptomatic therapy; (2) Time to and severity of motor complications may reflect a secondary measure of progression once type of initial symptomatic treatment is accounted for30, 31; (3) A potential beneficial effect of isradipine on disease progression could be masked by differential usage of ST. To account for this factor, we will evaluate differential use of ST by calculating the levodopa equivalent dosages between treatment groups32; (4) Incidence and severity of nonmotor symptoms, as these contribute disproportionately to quality of life and reflect clinically relevant outcomes in PD 33, 34, 35…”

“…Current therapy is limited to symptomatic treatment; however, the disease continues to progress with accumulation of significant disability, worsening quality of life, reduced productivity, nursing home placement, and increased mortality 4. Attempts to slow or modify disease progression in PD have resulted in mixed outcomes and no treatment has yet to definitively demonstrate disease modification (see Table 1 for recent disease‐modifying trials) 5, 6, 7, 8. Therefore, treatments that slow disease progression remain a major unmet therapeutic need in PD.…”

Algorithms for the treatment of motor problems in Parkinson's disease

“…The DATATOP study22 found that the use of selegiline delays the need for levodopa in early PD, but most investigators have interpreted this as a symptomatic effect caused by MAO‐B inhibition that delays dopaminergic elimination from dopaminergic synapses. However, two randomized double‐blind long‐term Scandinavian studies comparing selegiline to levodopa in early PD found that patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline 23, 24.…”