Efficacy of Isradipine in Early-Stage Parkinson Disease

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woman taking pills
Researchers assessed the effect of isradipine on clinical progression in previously untreated patients with early-stage PD.

Treatment with immediate-release isradipine, a dihydropyridine calcium-channel blocker, did not slow the clinical progression of early-onset Parkinson disease (PD) compared with placebo, according to study results published in the Annals of Internal Medicine.

Isradipine is approved for the treatment of hypertension, but animal models of PD showed it has neuroprotective effects. Furthermore, previous studies have reported a reduced risk for PD with dihydropyridines compared with other antihypertensive agents. The goal of the study was to assess the effect of isradipine on clinical progression, according to the Unified Parkinson’s Disease Rating Scale (UPDRS) in previously untreated patients with early-stage PD.

The multicenter, randomized, parallel-group, placebo-controlled trial included patients from 57 Parkinson Study Group sites in North America with a diagnosis of PD within the previous 3 years (early-stage PD). The participants were randomly assigned in 1:1 allocation to receive either 5 mg of immediate-release isradipine, twice daily, or matching placebo for 36 months. The primary outcome was the change in UPDRS parts I to III score from baseline to 36 months.

The study cohort included 170 participants (mean age, 62.1 years; 71.8% men) treated with isradipine and 166 participants (mean age, 61.6 years; 65.1% men) in the placebo group. A total of 18 patients withdrew from the study; thus, 170 patients in the isradipine group and 166 patients in the placebo group completed both baseline and final evaluations.

The estimated least-squares mean changes from baseline to 3 years in the total UPDRS score were 2.99 (95% CI, 0.95-5.03) points in the isradipine group and 3.26 (95% CI, 1.25-5.26) points in the placebo group (least-squares mean adjusted difference, −0.27; 95% CI, −3.02 to 2.48; P =.85). Statistical adjustment for antiparkinson medication use did not change the findings.

Analyses of the key secondary outcome measures and all other secondary outcomes showed no effect of isradipine treatment.

The most common adverse effects that were more frequent in the isradipine group than the placebo group were dizziness (24.7% vs 15.7%, respectively) and peripheral edema (18.2% vs 5.4%, respectively). Ten adverse events led to discontinuation of treatment, including 7 events in the isradipine group and 3 events in the placebo group.

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The researchers acknowledged several study limitations, including possible selection of a too low a dose of isradipine to provide benefit, lack of direct measurement of target calcium-channel engagement in human brains. The researchers also note that it is possible treatment was given too late and that initiating isradipine at an earlier stage of the disease would be more effective.

“[T]reatment with 5 mg of immediate-release isradipine twice daily did not slow the clinical progression of early-stage PD, as measured by the change in the UPDRS score and various other measures and instruments,” conclude the researchers.


The Parkinson Study Group STEADY-PD III Investigators. Isradipine versus placebo in early Parkinson disease: a randomized trial [published online March 31, 2020]. Ann Intern Med. doi:10.7326/M19-2534.