Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial
Parkinson Study Group STEADY-PD III Investigators, Tanya Simuni, David Oakes, Kevin Biglan, Wendy R. Galpern, Robert Hauser, Karen Hodgeman, Elise Kayson, Daniel Kinel, Anthony Lang, Codrin Lungu, Saloni Sharma, Ira Shoulson, Christopher G. Tarolli, Dalton J. Surmeier, Charles Venuto, Robert Holloway, Katie Kompoliti, Irene Richard, Ruth Schneider, Marian Evatt, Vanessa Hinson, Alok Sahay, Irene Litvan, Eris S. Farbman, Brad Racette, Karen Blindauer, Karen Thomas, Cheryl Water, Connie Marras, Corneliu C. Luca, Albert Hung, Andre Deik, Deborah Burke, Cindy Zadikoff, Michel Panisset, Marcie Rabin, Matthew Brodsky, Kelly Mills, Alexander Shtilbans, Era Hanspal, Chadwick W. Christine, Thyagarajan Subramanian, Mya Caryn Schiess, Rajeev Kumar, Kelvin L. Chou, Binit Shah, Mark Guttman, Holly Shill, John Slevin, John L. Goudreau, Ariane Park, John Bertoni, Marie H. Saint-Hilaire, Natividad Stover, Camila Aquino, David Shprecher, Anwar Ahmed, Lisa Shulman, Sotirios A. Parashos, Stephen Lee, Paul Tuite, Melanie Langlois, Fabio Danisi, Pinky Agarwal, Tiago Mestre, David Russell, Daniel Truong, Neal Hermanowicz, Richard Zweig, Oksana Suchowersky, Justyna R. Sarna, G. Webster Ross, Lucia Blasucci, Carol Zimmerman, Shonna Jenkins, Erin Neefus, Mary Pecoraro, Lynn Wheeler, Lisa Richardson, Amber Ratel, Julie Racioppa, Grace Bwala, Suzanne Reichwein, Claudia Rocha, Karen Williams, Kelli Keith, Emily Carman, Sharon Evans, Aaron Daley, Kala Venkiteswaran, Vicki Ephron, Karen Ortiz, Angela Stovall, Molly Goddard, Renee Wagner, Katherine Ambrogi, Carolyn Peterson, Cathi A. Thomas, Michelle Cines, Patricia Ede, Pauline LeBlanc, Susan Rolandelli, Bryan Lewis, Anna Fierro, Breanna Chew, Jeanne McGee, Paul McCann, Michael Matwichyna, Arthur Watts, Michael McDermott, Shirley Eberly, Brittany Greco, Susan Henderson, Jillian Lowell, Andrew Siderowf, Rick Chappell, Jay Phillips, Kapil D. Sethi, William B. White, Parkinson Study Group STEADY-PD III Investigators, Tanya Simuni, David Oakes, Kevin Biglan, Wendy R. Galpern, Robert Hauser, Karen Hodgeman, Elise Kayson, Daniel Kinel, Anthony Lang, Codrin Lungu, Saloni Sharma, Ira Shoulson, Christopher G. Tarolli, Dalton J. Surmeier, Charles Venuto, Robert Holloway, Katie Kompoliti, Irene Richard, Ruth Schneider, Marian Evatt, Vanessa Hinson, Alok Sahay, Irene Litvan, Eris S. Farbman, Brad Racette, Karen Blindauer, Karen Thomas, Cheryl Water, Connie Marras, Corneliu C. Luca, Albert Hung, Andre Deik, Deborah Burke, Cindy Zadikoff, Michel Panisset, Marcie Rabin, Matthew Brodsky, Kelly Mills, Alexander Shtilbans, Era Hanspal, Chadwick W. Christine, Thyagarajan Subramanian, Mya Caryn Schiess, Rajeev Kumar, Kelvin L. Chou, Binit Shah, Mark Guttman, Holly Shill, John Slevin, John L. Goudreau, Ariane Park, John Bertoni, Marie H. Saint-Hilaire, Natividad Stover, Camila Aquino, David Shprecher, Anwar Ahmed, Lisa Shulman, Sotirios A. Parashos, Stephen Lee, Paul Tuite, Melanie Langlois, Fabio Danisi, Pinky Agarwal, Tiago Mestre, David Russell, Daniel Truong, Neal Hermanowicz, Richard Zweig, Oksana Suchowersky, Justyna R. Sarna, G. Webster Ross, Lucia Blasucci, Carol Zimmerman, Shonna Jenkins, Erin Neefus, Mary Pecoraro, Lynn Wheeler, Lisa Richardson, Amber Ratel, Julie Racioppa, Grace Bwala, Suzanne Reichwein, Claudia Rocha, Karen Williams, Kelli Keith, Emily Carman, Sharon Evans, Aaron Daley, Kala Venkiteswaran, Vicki Ephron, Karen Ortiz, Angela Stovall, Molly Goddard, Renee Wagner, Katherine Ambrogi, Carolyn Peterson, Cathi A. Thomas, Michelle Cines, Patricia Ede, Pauline LeBlanc, Susan Rolandelli, Bryan Lewis, Anna Fierro, Breanna Chew, Jeanne McGee, Paul McCann, Michael Matwichyna, Arthur Watts, Michael McDermott, Shirley Eberly, Brittany Greco, Susan Henderson, Jillian Lowell, Andrew Siderowf, Rick Chappell, Jay Phillips, Kapil D. Sethi, William B. White
Abstract
Background: Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD).
Objective: To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD.
Design: Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842).
Setting: 57 Parkinson Study Group sites in North America.
Participants: Patients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment.
Intervention: 5 mg of immediate-release isradipine twice daily or placebo for 36 months.
Measurements: The primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures.
Results: 336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness.
Limitation: The isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects.
Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.
Primary funding source: National Institute of Neurological Disorders and Stroke.
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Source: PubMed