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Sample size calculations for clinical trials targeting tauopathies: a new potential disease target

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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.

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Acknowledgments

This study was funded by R01-DC12519 (PI Whitwell), R01-DC010367 (PI Josephs) and U01-AG06786 (PI Petersen).

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

The study was approved by the Mayo Clinic Institutional Review Board and was, therefore, performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects were consented for enrolment into the study.

Author information

Authors and Affiliations

  1. Department of Radiology, Mayo Clinic, Rochester, MN, 55905, USA

    Jennifer L. Whitwell, Matthew L. Senjem, Anthony J. Spychalla, Jeffrey L. Gunter & Clifford R. Jack Jr.

  2. Division of Speech Pathology, Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Joseph R. Duffy & Edythe A. Strand

  3. Division of Neuropsychology, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

    Mary M. Machulda

  4. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    Nirubol Tosakulwong & Stephen D. Weigand

  5. Department of Information Technology, Mayo Clinic, Rochester, MN, USA

    Matthew L. Senjem & Jeffrey L. Gunter

  6. Division of Behavioral Neurology, Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Ronald C. Petersen & Keith A. Josephs

Authors
  1. Jennifer L. Whitwell
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  2. Joseph R. Duffy
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  3. Edythe A. Strand
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  4. Mary M. Machulda
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  5. Nirubol Tosakulwong
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  6. Stephen D. Weigand
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  7. Matthew L. Senjem
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  8. Anthony J. Spychalla
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  9. Jeffrey L. Gunter
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  10. Ronald C. Petersen
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  11. Clifford R. Jack Jr.
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  12. Keith A. Josephs
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Corresponding author

Correspondence to Jennifer L. Whitwell.

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Whitwell, J.L., Duffy, J.R., Strand, E.A. et al. Sample size calculations for clinical trials targeting tauopathies: a new potential disease target. J Neurol 262, 2064–2072 (2015). https://doi.org/10.1007/s00415-015-7821-5

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  • DOI: https://doi.org/10.1007/s00415-015-7821-5

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