Parkinson's Cure Journey

Landmark 166 · Trial in people

LEAP: early vs delayed levodopa

Starting levodopa straight away did no better than starting it 40 weeks later, in 445 people. It eases symptoms but does not slow Parkinson's. There was no sign that it speeds the disease up at this dose.

In short

In 445 people, levodopa begun at once did no better after 80 weeks than levodopa begun after 40 weeks of placebo, so it does not slow the disease.

What it is
Trial in people
Outcome
Did not work
When
2019
Size
445 people · Phase 3
Research lane
Trial methods & regulation
Trial registry
ISRCTN30518857
Last checked
19 Oct 2026

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

C. V. M. Verschuur, R. M. A. de Bie and colleagues (LEAP Study Group), Netherlands. Funded by the Netherlands Organization for Health Research and Development and others. New England Journal of Medicine 2019;380:315–324. Trial number ISRCTN30518857.

What happened

ELLDOPA (landmark 161) left open whether levodopa slows or speeds progression. LEAP tested it with a delayed-start design and a longer period.

  • Design. 445 people with early Parkinson's (222 early start, 223 delayed start). Half took levodopa-carbidopa (100/25 mg, three times a day) for 80 weeks; half took placebo for 40 weeks and then levodopa for 40 weeks.
  • Result. The main measure was the change in total UPDRS from baseline to week 80: −1.0 points with early levodopa and −2.0 with delayed (difference 1.0, 95% CI −1.5 to 3.5, P=0.44). Dyskinesia and fluctuations did not differ. A secondary test did not clear the bar: between weeks 44 and 80 UPDRS rose faster in the early-start group (0.10 versus 0.03 points a week), so early levodopa was not shown to be non-inferior on that measure.
  • Follow-up. Of 321 people who reached 5 years, the adjusted UPDRS did not differ between groups at 3 years (P=0.18) or 5 years (P=0.07). Dyskinesia at 5 years: 46/160 early versus 62/161 delayed (P=0.06) (Frequin et al., Mov Disord 2024).
  • Limits. Low dose and short period; the authors said higher doses or longer use might need testing.

Why it moved us toward a cure

It found no sign that levodopa harms the disease course at this dose (the main measure and the 5-year follow-up showed no difference), and it showed once more that symptom drugs do not slow Parkinson's.

It tested whether starting levodopa (landmark 285) early changes the course of the disease.

Outcome

Dead end as a disease-slowing idea. Superseded the doubt left by ELLDOPA.

Sources

How it connects

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