Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study

Jane S. Paulsen, Jeffrey D. Long, Hans J. Johnson, Elizabeth H. Aylward, Christopher A. Ross, Janet K. Williams, Martha A. Nance, Cheryl J. Erwin, Holly J. Westervelt, Deborah L. Harrington, H. Jeremy Bockholt, Ying Zhang, Elizabeth A. McCusker, Edmond M. Chiu, Peter K. Panegyres, Stephen Cross, Patricia Ryan, Eric A. Epping, Joy Preston, Anita GohStephanie Antonopoulos, Samantha Loi, Lynn Raymond, Joji Decolongon, Mannie Fan, Allison Coleman, William M. Mallone, Greg Suter, Mark Varvaris, Nadine Yoritomo, Jane Griffith, Clement Loy, David Gunn, Mark Guttman, Alanna Sheinberg, Albie Law, Kimberly Quaid, Melissa Wesson, Joanne Wojcieszek, Joel Perlmutter, Stacey Barton, Shineeka Smith, Roger A. Barker, Sarah Mason, Natalie Valle Guzman, Susan Perlman, Brian Clemente, Randi Jones, Cathy Wood-Siverio, Stewart A. Factor, Ali Samii, Alma Macaraeg, Joseph Lee, Maria Tedesco, Brenton Maxwell, Rajeev Kumar, Diane Erickson, Breanna Nickels, Frederick Marshall, Amy Chesire, Mary Wodarski, Charlyne Hickey, Michael D. Geschwind, Sharon Sha, Gabriela Satris, Anwar Ahmed, Christine Reece, Alex Bura, Lyla Mourany, Jagan Pillai, Pietro Mazzoni, Karen Marder, Paula Wasserman, David Craufurd, Judith Bek, Elizabeth Howard, Tom Warner, Maggie Burrows, Michael Orth, Sigurd Süßmuth, Katrin Barth, Sonja Trautmann, Daniela Schwenk, Carolin Eschenbach, Vicki Wheelock, Lisa Kjer, Amanda Martin, Sarah Farias, Zosia Miedzybrodzka, Daniela Rae, Mariella D'Alessandro, Oksana Suchowersky, Phyllis Chua, Angela Komiti, Diana Rosas, Anne Rosser, Kathy Price, Sarah Hunt, Joseph Jankovic, William Ondo, Wayne Martin, Pamela King, Marguerite Wieler, Satwinder Sran, Justo Garcia de Yébenes, Richard Dubinsky

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington's disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7-12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

Original languageEnglish (US)
Article numberArticle 78
JournalFrontiers in Aging Neuroscience
Volume6
Issue numberAPR
DOIs
StatePublished - Jan 1 2014

Fingerprint

Huntington Disease
Biomarkers
Clinical Trials
Disease Progression
Outcome Assessment (Health Care)
Neurodegenerative Diseases
Documentation
Sample Size
Observational Studies
Psychiatry
Consensus

Keywords

  • Clinical trials
  • Huntington disease
  • Natural history
  • Neurodegenerative disorders
  • Outcome measures
  • PREDICT-HD
  • Premanifest

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

Paulsen, J. S., Long, J. D., Johnson, H. J., Aylward, E. H., Ross, C. A., Williams, J. K., ... Dubinsky, R. (2014). Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study. Frontiers in Aging Neuroscience, 6(APR), [Article 78]. https://doi.org/10.3389/fnagi.2014.00078

Clinical and biomarker changes in premanifest Huntington disease show trial feasibility : A decade of the PREDICT-HD study. / Paulsen, Jane S.; Long, Jeffrey D.; Johnson, Hans J.; Aylward, Elizabeth H.; Ross, Christopher A.; Williams, Janet K.; Nance, Martha A.; Erwin, Cheryl J.; Westervelt, Holly J.; Harrington, Deborah L.; Bockholt, H. Jeremy; Zhang, Ying; McCusker, Elizabeth A.; Chiu, Edmond M.; Panegyres, Peter K.; Cross, Stephen; Ryan, Patricia; Epping, Eric A.; Preston, Joy; Goh, Anita; Antonopoulos, Stephanie; Loi, Samantha; Raymond, Lynn; Decolongon, Joji; Fan, Mannie; Coleman, Allison; Mallone, William M.; Suter, Greg; Varvaris, Mark; Yoritomo, Nadine; Griffith, Jane; Loy, Clement; Gunn, David; Guttman, Mark; Sheinberg, Alanna; Law, Albie; Quaid, Kimberly; Wesson, Melissa; Wojcieszek, Joanne; Perlmutter, Joel; Barton, Stacey; Smith, Shineeka; Barker, Roger A.; Mason, Sarah; Guzman, Natalie Valle; Perlman, Susan; Clemente, Brian; Jones, Randi; Wood-Siverio, Cathy; Factor, Stewart A.; Samii, Ali; Macaraeg, Alma; Lee, Joseph; Tedesco, Maria; Maxwell, Brenton; Kumar, Rajeev; Erickson, Diane; Nickels, Breanna; Marshall, Frederick; Chesire, Amy; Wodarski, Mary; Hickey, Charlyne; Geschwind, Michael D.; Sha, Sharon; Satris, Gabriela; Ahmed, Anwar; Reece, Christine; Bura, Alex; Mourany, Lyla; Pillai, Jagan; Mazzoni, Pietro; Marder, Karen; Wasserman, Paula; Craufurd, David; Bek, Judith; Howard, Elizabeth; Warner, Tom; Burrows, Maggie; Orth, Michael; Süßmuth, Sigurd; Barth, Katrin; Trautmann, Sonja; Schwenk, Daniela; Eschenbach, Carolin; Wheelock, Vicki; Kjer, Lisa; Martin, Amanda; Farias, Sarah; Miedzybrodzka, Zosia; Rae, Daniela; D'Alessandro, Mariella; Suchowersky, Oksana; Chua, Phyllis; Komiti, Angela; Rosas, Diana; Rosser, Anne; Price, Kathy; Hunt, Sarah; Jankovic, Joseph; Ondo, William; Martin, Wayne; King, Pamela; Wieler, Marguerite; Sran, Satwinder; de Yébenes, Justo Garcia; Dubinsky, Richard.

In: Frontiers in Aging Neuroscience, Vol. 6, No. APR, Article 78, 01.01.2014.

Research output: Contribution to journalArticle

Paulsen, JS, Long, JD, Johnson, HJ, Aylward, EH, Ross, CA, Williams, JK, Nance, MA, Erwin, CJ, Westervelt, HJ, Harrington, DL, Bockholt, HJ, Zhang, Y, McCusker, EA, Chiu, EM, Panegyres, PK, Cross, S, Ryan, P, Epping, EA, Preston, J, Goh, A, Antonopoulos, S, Loi, S, Raymond, L, Decolongon, J, Fan, M, Coleman, A, Mallone, WM, Suter, G, Varvaris, M, Yoritomo, N, Griffith, J, Loy, C, Gunn, D, Guttman, M, Sheinberg, A, Law, A, Quaid, K, Wesson, M, Wojcieszek, J, Perlmutter, J, Barton, S, Smith, S, Barker, RA, Mason, S, Guzman, NV, Perlman, S, Clemente, B, Jones, R, Wood-Siverio, C, Factor, SA, Samii, A, Macaraeg, A, Lee, J, Tedesco, M, Maxwell, B, Kumar, R, Erickson, D, Nickels, B, Marshall, F, Chesire, A, Wodarski, M, Hickey, C, Geschwind, MD, Sha, S, Satris, G, Ahmed, A, Reece, C, Bura, A, Mourany, L, Pillai, J, Mazzoni, P, Marder, K, Wasserman, P, Craufurd, D, Bek, J, Howard, E, Warner, T, Burrows, M, Orth, M, Süßmuth, S, Barth, K, Trautmann, S, Schwenk, D, Eschenbach, C, Wheelock, V, Kjer, L, Martin, A, Farias, S, Miedzybrodzka, Z, Rae, D, D'Alessandro, M, Suchowersky, O, Chua, P, Komiti, A, Rosas, D, Rosser, A, Price, K, Hunt, S, Jankovic, J, Ondo, W, Martin, W, King, P, Wieler, M, Sran, S, de Yébenes, JG & Dubinsky, R 2014, 'Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study', Frontiers in Aging Neuroscience, vol. 6, no. APR, Article 78. https://doi.org/10.3389/fnagi.2014.00078
Paulsen, Jane S. ; Long, Jeffrey D. ; Johnson, Hans J. ; Aylward, Elizabeth H. ; Ross, Christopher A. ; Williams, Janet K. ; Nance, Martha A. ; Erwin, Cheryl J. ; Westervelt, Holly J. ; Harrington, Deborah L. ; Bockholt, H. Jeremy ; Zhang, Ying ; McCusker, Elizabeth A. ; Chiu, Edmond M. ; Panegyres, Peter K. ; Cross, Stephen ; Ryan, Patricia ; Epping, Eric A. ; Preston, Joy ; Goh, Anita ; Antonopoulos, Stephanie ; Loi, Samantha ; Raymond, Lynn ; Decolongon, Joji ; Fan, Mannie ; Coleman, Allison ; Mallone, William M. ; Suter, Greg ; Varvaris, Mark ; Yoritomo, Nadine ; Griffith, Jane ; Loy, Clement ; Gunn, David ; Guttman, Mark ; Sheinberg, Alanna ; Law, Albie ; Quaid, Kimberly ; Wesson, Melissa ; Wojcieszek, Joanne ; Perlmutter, Joel ; Barton, Stacey ; Smith, Shineeka ; Barker, Roger A. ; Mason, Sarah ; Guzman, Natalie Valle ; Perlman, Susan ; Clemente, Brian ; Jones, Randi ; Wood-Siverio, Cathy ; Factor, Stewart A. ; Samii, Ali ; Macaraeg, Alma ; Lee, Joseph ; Tedesco, Maria ; Maxwell, Brenton ; Kumar, Rajeev ; Erickson, Diane ; Nickels, Breanna ; Marshall, Frederick ; Chesire, Amy ; Wodarski, Mary ; Hickey, Charlyne ; Geschwind, Michael D. ; Sha, Sharon ; Satris, Gabriela ; Ahmed, Anwar ; Reece, Christine ; Bura, Alex ; Mourany, Lyla ; Pillai, Jagan ; Mazzoni, Pietro ; Marder, Karen ; Wasserman, Paula ; Craufurd, David ; Bek, Judith ; Howard, Elizabeth ; Warner, Tom ; Burrows, Maggie ; Orth, Michael ; Süßmuth, Sigurd ; Barth, Katrin ; Trautmann, Sonja ; Schwenk, Daniela ; Eschenbach, Carolin ; Wheelock, Vicki ; Kjer, Lisa ; Martin, Amanda ; Farias, Sarah ; Miedzybrodzka, Zosia ; Rae, Daniela ; D'Alessandro, Mariella ; Suchowersky, Oksana ; Chua, Phyllis ; Komiti, Angela ; Rosas, Diana ; Rosser, Anne ; Price, Kathy ; Hunt, Sarah ; Jankovic, Joseph ; Ondo, William ; Martin, Wayne ; King, Pamela ; Wieler, Marguerite ; Sran, Satwinder ; de Yébenes, Justo Garcia ; Dubinsky, Richard. / Clinical and biomarker changes in premanifest Huntington disease show trial feasibility : A decade of the PREDICT-HD study. In: Frontiers in Aging Neuroscience. 2014 ; Vol. 6, No. APR.
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T1 - Clinical and biomarker changes in premanifest Huntington disease show trial feasibility

T2 - A decade of the PREDICT-HD study

AU - Paulsen, Jane S.

AU - Long, Jeffrey D.

AU - Johnson, Hans J.

AU - Aylward, Elizabeth H.

AU - Ross, Christopher A.

AU - Williams, Janet K.

AU - Nance, Martha A.

AU - Erwin, Cheryl J.

AU - Westervelt, Holly J.

AU - Harrington, Deborah L.

AU - Bockholt, H. Jeremy

AU - Zhang, Ying

AU - McCusker, Elizabeth A.

AU - Chiu, Edmond M.

AU - Panegyres, Peter K.

AU - Cross, Stephen

AU - Ryan, Patricia

AU - Epping, Eric A.

AU - Preston, Joy

AU - Goh, Anita

AU - Antonopoulos, Stephanie

AU - Loi, Samantha

AU - Raymond, Lynn

AU - Decolongon, Joji

AU - Fan, Mannie

AU - Coleman, Allison

AU - Mallone, William M.

AU - Suter, Greg

AU - Varvaris, Mark

AU - Yoritomo, Nadine

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AU - Loy, Clement

AU - Gunn, David

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AU - Wesson, Melissa

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AU - Perlmutter, Joel

AU - Barton, Stacey

AU - Smith, Shineeka

AU - Barker, Roger A.

AU - Mason, Sarah

AU - Guzman, Natalie Valle

AU - Perlman, Susan

AU - Clemente, Brian

AU - Jones, Randi

AU - Wood-Siverio, Cathy

AU - Factor, Stewart A.

AU - Samii, Ali

AU - Macaraeg, Alma

AU - Lee, Joseph

AU - Tedesco, Maria

AU - Maxwell, Brenton

AU - Kumar, Rajeev

AU - Erickson, Diane

AU - Nickels, Breanna

AU - Marshall, Frederick

AU - Chesire, Amy

AU - Wodarski, Mary

AU - Hickey, Charlyne

AU - Geschwind, Michael D.

AU - Sha, Sharon

AU - Satris, Gabriela

AU - Ahmed, Anwar

AU - Reece, Christine

AU - Bura, Alex

AU - Mourany, Lyla

AU - Pillai, Jagan

AU - Mazzoni, Pietro

AU - Marder, Karen

AU - Wasserman, Paula

AU - Craufurd, David

AU - Bek, Judith

AU - Howard, Elizabeth

AU - Warner, Tom

AU - Burrows, Maggie

AU - Orth, Michael

AU - Süßmuth, Sigurd

AU - Barth, Katrin

AU - Trautmann, Sonja

AU - Schwenk, Daniela

AU - Eschenbach, Carolin

AU - Wheelock, Vicki

AU - Kjer, Lisa

AU - Martin, Amanda

AU - Farias, Sarah

AU - Miedzybrodzka, Zosia

AU - Rae, Daniela

AU - D'Alessandro, Mariella

AU - Suchowersky, Oksana

AU - Chua, Phyllis

AU - Komiti, Angela

AU - Rosas, Diana

AU - Rosser, Anne

AU - Price, Kathy

AU - Hunt, Sarah

AU - Jankovic, Joseph

AU - Ondo, William

AU - Martin, Wayne

AU - King, Pamela

AU - Wieler, Marguerite

AU - Sran, Satwinder

AU - de Yébenes, Justo Garcia

AU - Dubinsky, Richard

PY - 2014/1/1

Y1 - 2014/1/1

N2 - There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington's disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7-12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

AB - There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington's disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7-12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

KW - Clinical trials

KW - Huntington disease

KW - Natural history

KW - Neurodegenerative disorders

KW - Outcome measures

KW - PREDICT-HD

KW - Premanifest

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