DATATOP: deprenyl

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

The Parkinson Study Group, a North American network of investigators at 28 US and Canadian sites; Ira Shoulson wrote the 1989 design report. DATATOP stands for Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism.

What happened

The trial began in 1987. 800 people with early, untreated Parkinson's were randomised in a 2x2 design to deprenyl (also called selegiline, 10 mg a day), vitamin E (tocopherol, 2,000 IU a day), both, or placebo. The main measure was how long until a person's disability was bad enough to need levodopa. An interim report in 1989 (average 12 months of follow-up) found 97 deprenyl recipients reached that point against 176 non-recipients (hazard ratio 0.43, 95% CI 0.33–0.55). The 1993 report (mean follow-up 14 months) gave a hazard ratio of 0.50 (95% CI 0.41–0.62, P < 0.001) and a median delay of about nine months; vitamin E had no benefit and did not interact with deprenyl. Scores improved in the first three months on deprenyl and worsened after the drug was withdrawn.

Why it moved us toward a cure

It was the first time a large, placebo-controlled trial tested whether a drug could slow Parkinson's itself, not just ease it, and it set the template (early untreated patients, "time to needing levodopa") for later trials. Its limits taught the field a second lesson. Deprenyl improved clinical scores within a month, and a 1994 re-evaluation (Ward, J Neurol Neurosurg Psychiatry) argued the lower chance of needing levodopa more likely reflected direct symptom relief than slower disease. Trial designs that separate symptom effects from true slowing, such as the delayed-start design in landmark 62, came from this problem.

It was run by the Parkinson Study Group (landmark 277).

Outcome

Superseded. Deprenyl stayed in use as a symptom treatment; it was not established as slowing Parkinson's. The 1996 follow-up of the 310 people who had not needed levodopa found the early advantage of deprenyl was not sustained (hazard ratio 1.43 for reaching the end point later, 95% CI 0.98–2.09, with the deprenyl group sicker at baseline), and early deprenyl did not reduce later levodopa side effects. Later, larger trials of antioxidants, such as coenzyme Q10 in QE3, were also negative. See also the table in dead ends.

Sources

• Parkinson Study Group, N Engl J Med 1989;321:1364–1371 (interim)
• Parkinson Study Group, N Engl J Med 1993;328:176–183, DOI 10.1056/nejm199301213280305 (summary read via Europe PMC)
• Parkinson Study Group, Acta Neurol Scand Suppl 1991;136:79–86
• Parkinson Study Group, DATATOP design, Arch Neurol 1989;46:1052–1060
• Ward CD, "Does selegiline delay progression of Parkinson's disease? A critical re-evaluation of the DATATOP study," J Neurol Neurosurg Psychiatry 1994;57:217–220, DOI 10.1136/jnnp.57.2.217
• Parkinson Study Group, Ann Neurol 1996;39:29–36 and 39:37–45
• Holford, Chan, Nutt, PAGE 2004 abstract (modelling of DATATOP data)
• Not yet verified: why deprenyl was chosen (the MPTP/MAO-B link, see landmark 2); any regulator ruling on a neuroprotection claim; the Holford modelling abstract was not re-read. Abstracts only; full texts not read.