Mitochondrial Biomarkers in Huntington's Disease

Longitudinal Biospecimen Collection for Mitochondrial Metabolomics in Huntington's Disease

The objective of this study is to discover a panel of mitochondrial metabolomics biomarkers for Huntington's disease.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Diagnostic test: lumbar puncture

Detailed Description

This investigator-initiated, single-site longitudinal study seeks to assess the utility of mitochondrial metabolomics -- panels of small molecules that affect mitochondrial function -- to diagnose pre-symptomatic, pre-manifest, and symptomatic Huntington's disease and serve as biomarkers for HD severity and progression. It also seeks to demonstrate that this novel biomarker in the blood has comparable value to the same analysis in spinal fluid. This research study involves 3-4 visits over 18 months. Forty volunteers with HD and 25 volunteers without HD will be included. Volunteers who have HD will have a physical examination and blood draw at each study visit. Some participants will also volunteer for optional lumbar puncture.

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of people with HD and controls without HD

Description

Inclusion Criteria:

• Age 20 to 85
• Montreal Cognitive Assessment score >10
• HD subjects had onset of HD symptoms after the age of 20
• HD subjects with Diagnostic Confidence Level (DCL) of 0-3 (pre-symptomatic or pre-manifest) must have at least 40 CAG repeats on one HTT allele
• HD subjects with Diagnostic Confidence Level (DCL) of 4 (manifest) must have at least 36 CAG repeats on one HTT allele
• Controls are asymptomatic without family history of HD or have <36 CAG repeats on both HTT alleles with family history of HD

Exclusion Criteria:

• HD subjects who did not already have genetic testing are excluded from this study
• Pregnancy or plans to become pregnant during the study
• Investigational drugs within 3 months of screening visit
• Alcohol or illicit drug abuse or dependence
• Other genetic or neurological disorders
• Other medical or psychiatric illness that in the investigator's judgement will prevent ability to tolerate or undergo study procedures
• For those volunteering for lumbar puncture (LP), bleeding disorders or excessive bleeding, anticoagulation, aspirin if unable to safely stop taking it at least 7 days prior to LP, other antiplatelet medications, inability to tolerate LP, allergy to local anesthetic or chlorhexidine, major lumbar spine deformity, low platelets or abnormal coagulation factors PT/APTT

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Huntington's disease (HD); people with HD	Diagnostic test: lumbar puncture; Some participants will have an optional lumbar puncture
Controls without HD; people without HD	Diagnostic test: lumbar puncture; Some participants will have an optional lumbar puncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Unified Huntington Disease Rating Scale (UHDRS) and UHDRS sub-sections	This is a questionnaire and neurological examination. Lower values are better than higher values.	At baseline, 9 months, and 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montreal Cognitive Assessment (MoCA)	Zero to 30 point cognitive scale. Higher values are better than lower values.	At baseline, 9 months, and 18 months

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); The Cleveland Clinic; Case Western Reserve University
• Investigators: Principal Investigator: Xin Qi, PhD, Case Western Reserve University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 4, 2019
• Primary Completion (ACTUAL): February 28, 2022
• Study Completion (ACTUAL): February 28, 2022

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (ACTUAL): August 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 9, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: biomarker; Huntington disease; Huntington's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: 20181082; 1R21NS107897-01A1 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No