Huntington's Disease Young Adult Study 2.0

NCT06391619 | Active Not Recruiting

• 1 other identifier: 145646
• Study Type: observational
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn about the first signs of disease in young adult carriers of the gene for Huntington's disease. The main questions to answer are:

• what are the earliest signs of the disease?
• can we identify the best time to intervene with treatment to prevent or delay onset of symptoms?
• can we identify the most reliable markers of disease for use in prevention trials? Participants will undergo the following assessments:
• clinical examination
• cognitive and neuropsychiatric testing
• brain imaging
• biofluid sampling Researchers will compare gene carriers with matched controls to see if any of these measures show evidence of early disease effects.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (3)

• Brain volume in ml

  Global and regional measures of brain volume

  Baseline, 4.5 years, 6 years

• Biofluids in grams per litre

  Blood and CSF measures

  Baseline, 4.5 years, 6 years

• Cognition (raw scores)

  Cognitive tests including CANTAB and EMOTICOM

  Baseline, 4.5 years, 6 years

Study Arms (2)

Huntington's disease gene carriers

Individuals with a positive test for the HD gene who were more than 20 years from expected symptom onset at baseline assessment.

Other: No intervention

Controls

Healthy controls matched to the gene carrier group for age, sex and education

Other: No intervention

Interventions

No intervention OTHER

Study is observational

Controls; Huntington's disease gene carriers

Eligibility Criteria

• Age: 18 Years - 47 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Young adult Huntington's disease gene carriers and age-, sex- and education-matched controls between the ages of 18 and 47

You may qualify if:

• For the Healthy Control group, participants eligible are persons who meet the following criteria:
• Are capable of providing informed consent and
• Are capable of complying with study procedures and
• Are aged between 18-47 years old and
• Have no known family history of HD (gene negative); or
• Have known family history of HD but have been tested for the huntingtin gene CAG expansion and are not at genetic risk for HD (CAG \< 36\*) (family control or community control)
• For the Young Adult Premanifest HD group, participants eligible are persons who meet the following criteria:
• Are capable of providing informed consent and
• Are capable of complying with study procedures and
• Are aged between 18-47 years old and
• Have CAG expansion ≥ 40;
• New participants must have a DBS \<240

You may not qualify if:

• Current use of investigational drugs or participation in a clinical drug trial within 30 days prior to study visit; or b. Current intoxication, drug or alcohol abuse or dependence; or c. If using any antidepressant, psychoactive, psychotropic or other medications or nutraceuticals used to treat HD, the use of inappropriate (e.g., non-therapeutically high) or unstable dose within 30 days prior to study visit; or d. Significant medical, neurological or psychiatric co-morbidity likely, in the judgment of the Principal Investigator, to impair participant's ability to complete essential study procedures; or e. Predictable non-compliance as assessed by the Principal Investigator; or f. Inability or unwillingness to undertake any of the essential study procedures; or g. Needle phobia: or h. Contraindication to MRI, including, but not limited to, MR-incompatible pacemakers, recent metallic implants, foreign body in the eye or other indications, as assessed by a standard pre-MRI questionnaire;or i. Pregnant (as confirmed by urine pregnancy test); or j. Claustrophobia, or any other condition that would make the subject incapable of undergoing an MRI.
• For CSF collection:
• Needle phobia, frequent headache, significant lower spinal deformity or major surgery; or
• Antiplatelet or anticoagulant therapy within the 14 days prior to sampling visit, including but not limited to: aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban; or
• Clotting or bruising disorder; or
• Screening blood test results outside the clinical laboratory's normal range for the following: white cell count, neutrophil count, lymphocyte count, haemoglobin (Hb), platelets, prothrombin time (PT) or activated partial thromboplastin time (APTT); or
• Screening blood test results for C-reactive protein (CRP)\>2× upper limit of normal; or
• i any reason to suspect abnormal bleeding tendency, e.g. easy bruising, petechial rash; or ii any reason to suspect new focal neurological lesion, e.g. new headache, optic disc swelling, asymmetric focal long tract signs; or iii any other reason that, in the clinical judgment of the operator or the Principal Investigator, it is felt that lumbar puncture is unsafe.
• For Optional 7T MRI and MEG
• Contraindication to MRI, including, but not limited to, MR-incompatible pacemakers, recent metallic implants, foreign body in the eye or other indications, as assessed by a standard pre-MRI questionnaire; or
• Pregnant (as confirmed by urine pregnancy test); or
• Claustrophobia, or any other condition that would make the subject incapable of undergoing an MRI; or
• Tattoos that fall above the line defined by the crease of the elbow or on the genitals.

Sponsors & Collaborators

• University College, London: lead
• University of Iowa: collaborator
• University of Cambridge: collaborator
• University of Glasgow: collaborator

Study Sites (1)

University College London

London, WC1N 3BG, United Kingdom

Location

Related Publications (1)

• Scahill RI, Farag M, Murphy MJ, Hobbs NZ, Leocadi M, Langley C, Knights H, Ciosi M, Fayer K, Nakajima M, Thackeray O, Gobom J, Ronnholm J, Weiner S, Hassan YR, Ponraj NKP, Estevez-Fraga C, Parker CS, Malone IB, Hyare H, Long JD, Heslegrave A, Sampaio C, Zhang H, Robbins TW, Zetterberg H, Wild EJ, Rees G, Rowe JB, Sahakian BJ, Monckton DG, Langbehn DR, Tabrizi SJ. Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis. Nat Med. 2025 Mar;31(3):807-818. doi: 10.1038/s41591-024-03424-6. Epub 2025 Jan 17.

  PMID: 39825149 DERIVED

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: April 30, 2024
• Study Start: April 6, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)