Study protocol for the iMarkHD study in individuals with Huntington's disease

Daniel J van Wamelen; Naomi H Martin; Orsolya Makos; James Badenoch; Jose Manuel Valera-Bermejo; Monika Hartmann; Alay Rangel Cristales; Tobias C Wood; Mattia Veronese; Manuela Moretto; Fernando Zelaya; Flavio dell'Acqua; Owen O'Daly; David J Lythgoe; Cedric Ginestet; Federico Turkheimer; Nikki Palasits; Ladislav Mrzljak; John H Warner; Eugenii A Rabiner; Roger Gunn; Sarah J Tabrizi; Cristina Sampaio; Andrew Wood; Steven Cr Williams

doi:10.1177/18796397241288165

Study protocol for the iMarkHD study in individuals with Huntington's disease

Daniel J van Wamelen, Naomi H Martin, Orsolya Makos, James Badenoch, Jose Manuel Valera-Bermejo, Monika Hartmann, Alay Rangel Cristales, Tobias C Wood, Mattia Veronese, Manuela Moretto, Fernando Zelaya, Flavio dell'Acqua, Owen O'Daly, David J Lythgoe, Cedric Ginestet, Federico Turkheimer, Nikki Palasits, Ladislav Mrzljak, John H Warner, Eugenii A RabinerRoger Gunn, Sarah J Tabrizi, Cristina Sampaio, Andrew Wood, Steven Cr Williams

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. Objective: In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. Methods: Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. Results: Recruitment is currently active and started in September 2022. Conclusions: By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials.

Original language	English
Pages (from-to)	479-489
Number of pages	11
Journal	Journal of Huntington's Disease
Volume	13
Issue number	4
DOIs	https://doi.org/10.1177/18796397241288165
Publication status	Published - Nov 2024

Keywords

Huntington Disease/diagnostic imaging
Humans
Magnetic Resonance Imaging
Positron-Emission Tomography
Adult
Male
Female
Disease Progression
Middle Aged
Brain/diagnostic imaging
Biomarkers/blood
Phosphoric Diester Hydrolases/metabolism

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van Wamelen, D. J., Martin, N. H., Makos, O., Badenoch, J., Valera-Bermejo, J. M., Hartmann, M., Cristales, A. R., Wood, T. C., Veronese, M., Moretto, M., Zelaya, F., dell'Acqua, F., O'Daly, O., Lythgoe, D. J., Ginestet, C., Turkheimer, F., Palasits, N., Mrzljak, L., Warner, J. H., ... Williams, S. C. (2024). Study protocol for the iMarkHD study in individuals with Huntington's disease. Journal of Huntington's Disease, 13(4), 479-489. https://doi.org/10.1177/18796397241288165

@article{ccf474bf30f446839c0f7ba64aafad7c,

title = "Study protocol for the iMarkHD study in individuals with Huntington's disease",

abstract = " Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. Objective: In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. Methods: Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. Results: Recruitment is currently active and started in September 2022. Conclusions: By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials. ",

keywords = "Huntington Disease/diagnostic imaging, Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Adult, Male, Female, Disease Progression, Middle Aged, Brain/diagnostic imaging, Biomarkers/blood, Phosphoric Diester Hydrolases/metabolism",

author = "{van Wamelen}, {Daniel J} and Martin, {Naomi H} and Orsolya Makos and James Badenoch and Valera-Bermejo, {Jose Manuel} and Monika Hartmann and Cristales, {Alay Rangel} and Wood, {Tobias C} and Mattia Veronese and Manuela Moretto and Fernando Zelaya and Flavio dell'Acqua and Owen O'Daly and Lythgoe, {David J} and Cedric Ginestet and Federico Turkheimer and Nikki Palasits and Ladislav Mrzljak and Warner, {John H} and Rabiner, {Eugenii A} and Roger Gunn and Tabrizi, {Sarah J} and Cristina Sampaio and Andrew Wood and Williams, {Steven Cr}",

year = "2024",

month = nov,

doi = "10.1177/18796397241288165",

language = "English",

volume = "13",

pages = "479--489",

journal = "Journal of Huntington's Disease",

issn = "1879-6397",

publisher = "IOS Press",

number = "4",

}

van Wamelen, DJ , Martin, NH , Makos, O , Badenoch, J , Valera-Bermejo, JM , Hartmann, M , Cristales, AR , Wood, TC , Veronese, M, Moretto, M, Zelaya, F , dell'Acqua, F , O'Daly, O , Lythgoe, DJ , Ginestet, C , Turkheimer, F, Palasits, N, Mrzljak, L, Warner, JH, Rabiner, EA, Gunn, R, Tabrizi, SJ, Sampaio, C, Wood, A & Williams, SC 2024, 'Study protocol for the iMarkHD study in individuals with Huntington's disease', Journal of Huntington's Disease, vol. 13, no. 4, pp. 479-489. https://doi.org/10.1177/18796397241288165

TY - JOUR

T1 - Study protocol for the iMarkHD study in individuals with Huntington's disease

AU - van Wamelen, Daniel J

AU - Martin, Naomi H

AU - Makos, Orsolya

AU - Badenoch, James

AU - Valera-Bermejo, Jose Manuel

AU - Hartmann, Monika

AU - Cristales, Alay Rangel

AU - Wood, Tobias C

AU - Veronese, Mattia

AU - Moretto, Manuela

AU - Zelaya, Fernando

AU - dell'Acqua, Flavio

AU - O'Daly, Owen

AU - Lythgoe, David J

AU - Ginestet, Cedric

AU - Turkheimer, Federico

AU - Palasits, Nikki

AU - Mrzljak, Ladislav

AU - Warner, John H

AU - Rabiner, Eugenii A

AU - Gunn, Roger

AU - Tabrizi, Sarah J

AU - Sampaio, Cristina

AU - Wood, Andrew

AU - Williams, Steven Cr

PY - 2024/11

Y1 - 2024/11

N2 - Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. Objective: In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. Methods: Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. Results: Recruitment is currently active and started in September 2022. Conclusions: By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials.

AB - Background: Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the huntingtin gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. Objective: In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. Methods: Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. Results: Recruitment is currently active and started in September 2022. Conclusions: By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials.

KW - Huntington Disease/diagnostic imaging

KW - Humans

KW - Magnetic Resonance Imaging

KW - Positron-Emission Tomography

KW - Adult

KW - Male

KW - Female

KW - Disease Progression

KW - Middle Aged

KW - Brain/diagnostic imaging

KW - Biomarkers/blood

KW - Phosphoric Diester Hydrolases/metabolism

U2 - 10.1177/18796397241288165

DO - 10.1177/18796397241288165

M3 - Article

C2 - 39973385

SN - 1879-6397

VL - 13

SP - 479

EP - 489

JO - Journal of Huntington's Disease

JF - Journal of Huntington's Disease

IS - 4

ER -

Study protocol for the iMarkHD study in individuals with Huntington's disease

Abstract

Keywords

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