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JAMA Neurol. 2014 Jun;71(6):710-6. doi: 10.1001/jamaneurol.2014.391.

Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.

Collaborators (231)

Gross CR, Chen T, Levy DE, Rodnitzky RL, Welch KM, Beal M, Cummings JL, Geffen D, Fahn S, Levin B, Katz RG, Marin DB, Olanow CW, Martin JC, McDonald W, Murphy D, Piantadosi S, Powers WJ, Thal LJ, Wichman A, Marler J, Odenkirchen J, Ravina B, Kieburtz K, Tilley B, Shannon K, Tanner C, Deppen P, Dewey RB Jr, Hayward B, Scott B, Field J, Brodsky M, Andrews P, Manyam B, Whetteckey J, Rao J, Cook M, Aminoff MJ, Christine C, Roth J, Parashos S, Shannon K, Jaglin J, Singer C, Perez MA, Blenke A, Hauser R, Dunlop B, Lyons K, Parsons A, Leehey M, Shulman L, Pabst K, Elble R, Young C, Sethi K, Martin W, McInnes G, Calabrese VP, Roberge P, Hamill R, Homan C, Bodis-Wollner IG, Hayes E, Ross WG, Terashita S, Trugman J, Keller MF, Sage JI, Caputo D, Shearon D, Kelsey T, Feigin A, Watts RL, Stover N, McMurray R, Reichwein S, Simon D, Tarsy D, Scollins L, Tintner R, Hunter C, DeAngelis M, Burns RS, Shill H, Danielson J, Marlor L, Adler C, Lind M, Gorell J, Krstevska S, Schneider J, Gollomp S, Jefferson T, Coffey D, Lew MF, Kawai C, Turk M, Bower J, Handler J, Greenbaum K, Sabbagh M, Obradov Z, Huang P, Palesch Y, Kamp C, Shinaman A, Johnsen D, Brocht A, Goetz C, Fagan S, Gross CR, Chen DT, Levy DE, Marder K, Rodnitzky RL, Welch KM, Beal M, Fahn S, Levin B, Katz RG, Marin DB, Olanow CW, Martin JC, Murphy D, Powers WJ, Thal LJ, Wichman A, Marler J, Odenkirchen J, Shults C, Kieburtz K, Ravina B, Galpern WR, Tilley B, Shannon K, Tanner C, Wooten GF, Sage JI, Kosa E, Watts RL, Stover NR, McMurray R, Lew MF, Kawai C, Coffey D, LeBlanc P, Brodsky M, Andrews P, Siderowf A, Shulman L, Weiner WJ, Pabst K, Jaglin J, Suchowersky O, Derwent L, Rao J, Cook M, Aminoff MJ, Christine C, Roth J, Leehey M, Ross GW, Terashita S, Perez MA, Blenke A, Racette B, Deppen P, Elble R, Young C, Stewart T, Sethi K, Taylor J, Roberge P, Dewey RB Jr, Hayward B, Jankovic J, Hunter C, Keller MF, Jennings D, Kelsey T, Martin W, Savitt J, Dunlop B, Pahwa R, Lyons KE, Parsons A, Fang J, Shearon D, Feigin A, Marie M, Adler C, Lind M, Scott B, Field J, Nance M, Peterson S, Burns RS, Marlor L, Bodis-Wollner I, Hayes E, Sendek S, Gollomp S, Vernon G, Jefferson T, LeWitt P, DeAngelis M, Paul L, Gorell J, Krstevska S, Flewellen M, McCarthy S, Uitti R, Turk M, Bower J, Sabbagh M, Obradov Z, Juncos J, Musante ML, Fernandez H, Brown G, Huang P, Kamp C, Shinaman A, Brocht A, Bennett S, Baker D, Goetz C, Fagan S, Mauldin P.

Author information

1
Struthers Parkinson's Center, Golden Valley, Minnesota.
2
Division of Biostatistics, University of Texas at Houston.
3
Department of Neurology, University of Rochester, Rochester, New York.
4
State University of New York, Downstate Medical Center, Brooklyn.
5
The Parkinson's Institute and Clinical Center, Sunnyvale, California.
6
VA Pacific Islands Health Care System, Honolulu, Hawaii.
7
Department of Neurology, University of Maryland School of Medicine, Baltimore.

Abstract

IMPORTANCE:

Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.

OBJECTIVE:

To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.

DESIGN, SETTING, AND PARTICIPANTS:

Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.

INTERVENTIONS:

Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.

MAIN OUTCOMES AND MEASURES:

Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.

RESULTS:

After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.

CONCLUSIONS:

AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.

TRIAL REGISTRATION:

clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.

PMID:
24711047
PMCID:
PMC4188544
DOI:
10.1001/jamaneurol.2014.391
[Indexed for MEDLINE]
Free PMC Article

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