Study protocol of the HD-MED study aiming to personalize drug treatment in Huntington's disease: a longitudinal, observational study to assess medication use and efficacy in relation to pharmacogenetics.
Stephanie Feleus, Maaike van der Lee, Jesse J Swen, Raymund A C Roos, Susanne T de Bot
{"title":"Study protocol of the HD-MED study aiming to personalize drug treatment in Huntington's disease: a longitudinal, observational study to assess medication use and efficacy in relation to pharmacogenetics.","authors":"Stephanie Feleus, Maaike van der Lee, Jesse J Swen, Raymund A C Roos, Susanne T de Bot","doi":"10.1177/26330040231204643","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a hereditary, neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Currently, HD can only be managed symptomatically, including a large variety of prescribed drugs. Many HD patients experience negative medication effects (e.g. side effects or non-response). Pharmacogenetic (PGx) studies show how genetic variation affects both medication efficacy and toxicity and holds the potential to improve these outcomes of drug treatment.</p><p><strong>Primary objective: </strong>To classify the effect of the PGx profile of CYP2C19 and CYP2D6 in HD gene expansion carriers on negative medication effects of HD-related medication.</p><p><strong>Design: </strong>Multicenter, observational study with 1-year follow-up. Adult HD gene expansion carriers who use one or more HD-related medications are eligible to participate.</p><p><strong>Methods and analysis: </strong>A detailed overview of medication use, medication efficacy, and side effects is retrospectively and prospectively collected <i>via</i> medication diaries, questionnaires, phone calls, and pharmacy medication verification schemes. PGx analysis on whole blood-extracted DNA is performed with Agena Bioscience VeriDose<sup>®</sup> Core Panel and long-range polymerase chain reaction copy number variation analysis. Per the study protocol-defined negative medication effects in HD gene expansion carriers with a genotype predicted poor or ultrarapid metabolizer phenotype will be compared with HD gene expansion carriers with a predicted intermediate and normal metabolizer phenotype. Frequencies will be analyzed <i>via</i> χ<sup>2</sup> and logistic multivariate regression analysis. In addition, we summarize in this manuscript HD-relevant PGx prescription recommendations to improve drug therapy.</p><p><strong>Ethics: </strong>The original study protocol was approved by the medical research ethics committee Leiden Den Haag Delft on 26 November 2019.</p><p><strong>Discussion: </strong>HD-MED is a low-risk study that will generate personalized PGx results that can immediately be implemented in clinical practice, thus potentially improving pharmacovigilance and patients' quality of life.</p><p><strong>Registration: </strong>This study is registered in the International Clinical Trial Registry Platform under registration number NL8251, URL https://trialsearch.who.int/Trial2.aspx?TrialID=NL8251.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"4 ","pages":"26330040231204643"},"PeriodicalIF":0.0000,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634258/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic advances in rare disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/26330040231204643","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Huntington's disease (HD) is a hereditary, neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Currently, HD can only be managed symptomatically, including a large variety of prescribed drugs. Many HD patients experience negative medication effects (e.g. side effects or non-response). Pharmacogenetic (PGx) studies show how genetic variation affects both medication efficacy and toxicity and holds the potential to improve these outcomes of drug treatment.
Primary objective: To classify the effect of the PGx profile of CYP2C19 and CYP2D6 in HD gene expansion carriers on negative medication effects of HD-related medication.
Design: Multicenter, observational study with 1-year follow-up. Adult HD gene expansion carriers who use one or more HD-related medications are eligible to participate.
Methods and analysis: A detailed overview of medication use, medication efficacy, and side effects is retrospectively and prospectively collected via medication diaries, questionnaires, phone calls, and pharmacy medication verification schemes. PGx analysis on whole blood-extracted DNA is performed with Agena Bioscience VeriDose® Core Panel and long-range polymerase chain reaction copy number variation analysis. Per the study protocol-defined negative medication effects in HD gene expansion carriers with a genotype predicted poor or ultrarapid metabolizer phenotype will be compared with HD gene expansion carriers with a predicted intermediate and normal metabolizer phenotype. Frequencies will be analyzed via χ2 and logistic multivariate regression analysis. In addition, we summarize in this manuscript HD-relevant PGx prescription recommendations to improve drug therapy.
Ethics: The original study protocol was approved by the medical research ethics committee Leiden Den Haag Delft on 26 November 2019.
Discussion: HD-MED is a low-risk study that will generate personalized PGx results that can immediately be implemented in clinical practice, thus potentially improving pharmacovigilance and patients' quality of life.
Registration: This study is registered in the International Clinical Trial Registry Platform under registration number NL8251, URL https://trialsearch.who.int/Trial2.aspx?TrialID=NL8251.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
