Sample size calculations for clinical trials targeting tauopathies

a new potential disease target

Jennifer Lynn Whitwell, Joseph R. Duffy, Edythe A. Strand, Mary Margaret Machulda, Nirubol Tosakulwong, Stephen D. Weigand, Matthew L. Senjem, Anthony J. Spychalla, Jeffrey L. Gunter, Ronald Carl Petersen, Clifford R Jr. Jack, Keith Anthony Josephs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Disease-modifying therapies are being developed to target tau pathology, and should, therefore, be tested in primary tauopathies. We propose that progressive apraxia of speech should be considered one such target group. In this study, we investigate potential neuroimaging and clinical outcome measures for progressive apraxia of speech and determine sample size estimates for clinical trials. We prospectively recruited 24 patients with progressive apraxia of speech who underwent two serial MRI with an interval of approximately 2 years. Detailed speech and language assessments included the Apraxia of Speech Rating Scale and Motor Speech Disorders severity scale. Rates of ventricular expansion and rates of whole brain, striatal and midbrain atrophy were calculated. Atrophy rates across 38 cortical regions were also calculated and the regions that best differentiated patients from controls were selected. Sample size estimates required to power placebo-controlled treatment trials were calculated. The smallest sample size estimates were obtained with rates of atrophy of the precentral gyrus and supplementary motor area, with both measures requiring less than 50 subjects per arm to detect a 25 % treatment effect with 80 % power. These measures outperformed the other regional and global MRI measures and the clinical scales. Regional rates of cortical atrophy, therefore, provide the best outcome measures in progressive apraxia of speech. The small sample size estimates demonstrate feasibility for including progressive apraxia of speech in future clinical treatment trials targeting tau.

Original languageEnglish (US)
Pages (from-to)2064-2072
Number of pages9
JournalJournal of Neurology
Volume262
Issue number9
DOIs
StatePublished - Sep 22 2015

Fingerprint

Tauopathies
Apraxias
Sample Size
Clinical Trials
Atrophy
Motor Cortex
Outcome Assessment (Health Care)
Corpus Striatum
Speech Disorders
Frontal Lobe
Therapeutics
Mesencephalon
Neuroimaging
Language
Placebos
Pathology
Brain

Keywords

  • Apraxia of speech
  • Clinical treatment trials
  • MRI
  • PPAOS
  • Rates
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Sample size calculations for clinical trials targeting tauopathies : a new potential disease target. / Whitwell, Jennifer Lynn; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary Margaret; Tosakulwong, Nirubol; Weigand, Stephen D.; Senjem, Matthew L.; Spychalla, Anthony J.; Gunter, Jeffrey L.; Petersen, Ronald Carl; Jack, Clifford R Jr.; Josephs, Keith Anthony.

In: Journal of Neurology, Vol. 262, No. 9, 22.09.2015, p. 2064-2072.

Research output: Contribution to journalArticle

Whitwell, Jennifer Lynn ; Duffy, Joseph R. ; Strand, Edythe A. ; Machulda, Mary Margaret ; Tosakulwong, Nirubol ; Weigand, Stephen D. ; Senjem, Matthew L. ; Spychalla, Anthony J. ; Gunter, Jeffrey L. ; Petersen, Ronald Carl ; Jack, Clifford R Jr. ; Josephs, Keith Anthony. / Sample size calculations for clinical trials targeting tauopathies : a new potential disease target. In: Journal of Neurology. 2015 ; Vol. 262, No. 9. pp. 2064-2072.
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