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Examination of Quantitative Electroencephalographic (QEEG) Biomarkers in Huntington's Disease (HD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00670709
Recruitment Status : Completed
First Posted : May 2, 2008
Results First Posted : August 16, 2010
Last Update Posted : February 11, 2013
High Q Foundation
Information provided by (Responsible Party):
Andrew F. Leuchter, University of California, Los Angeles

Brief Summary:

The pace of basic science research defining the mechanisms of selective neuronal degeneration in Huntington disease (HD) has far exceeded the pace of translation of this information into clinically effective treatments for the disease. One reason for this bottleneck between bench and bedside is the paucity of available surrogate markers for HD. Identification of surrogate markers is critical for the design of future clinical trials. Such markers could provide a reliable signal of early brain dysfunction in HD and could be used as a biomarker in trials of agents that could prevent onset or delay progression of disease.

Frontal-subcortical networks are known to be affected in HD and contribute to the cognitive dysfunction characteristic of the disease. Quantitative EEG (QEEG) can be used to assess the integrity of this circuitry; characteristic QEEG abnormalities long have been known to be present in the early stages of the illness (Bylsma et al., 1994). More recent research has suggested that a comprehensive topographic approach to QEEG analysis may reveal additional changes in brain activity (Bellotti et al., 2004) that may be indicative of subclinical disease (de Tommaso et al., 2003). This proposal aims to determine whether quantitative EEG techniques can be used to identify HD-specific abnormalities and thus serve as surrogate markers of disease.

The goals of this pilot project are three-fold. First, we will determine if there are QEEG differences between normal control subjects and those with mild or moderate HD. Second, we will examine associations between severity of HD and the QEEG differences detected and determine if these QEEG differences are present when comparing the least affected HD subjects and normal controls. Third, we will examine associations between QEEG variables of interest and other clinical variables, including age of onset of symptoms, number of CAG repeats, severity of motor and behavioral symptoms as measured by the Unified Huntington Disease Rating Scale (UHDRS) subscores, and severity of cognitive impairment as measured by the cognitive subscore of the UHDRS and Mini-Mental State Examination (MMSE).

Condition or disease
Huntington's Disease

Detailed Description:

We will examine three subject groups in this study: those with mild HD, those with moderate HD, and normal controls. Fifteen subjects will be examined in each group, for an overall total of forty-five subjects. HD subjects will be recruited from the UCLA Huntington Disease Center of Excellence where they have been followed with serial neurologic examinations and completion of all portions of the UHDRS every 6-12 months. Subjects that have been given a diagnosis of HD based on appropriate motor signs and a confirmatory genetic test or a known family history of HD will be invited to participate. Healthy control subjects will be recruited from the clinic as well through spouses or other unaffected relatives of patients. In addition, control subject data acquired from previous studies will be used after matching for age. All subjects will be over the age of 21 and free of other medical illnesses that could also affect brain function and will be able to give informed consent. Mild HD is defined as having Total Functional Capacity [TFC] scores on the UHDRS of 11-13, moderate is defined as TFC of 7-10, and normal control subjects will be free of any neurologic or psychiatric illness. Subjects will be free of antipsychotic or antidepressant medications, benzodiazepines, or other medications known to affect central nervous system function for at least 10 days prior to QEEG examination.

All subjects will undergo QEEG recording in a manner similar to that employed clinically, using procedures that have been approved in other protocols by the UCLA Medical IRB and that are consistent with standard clinical EEG procedures promulgated by ABRET (American Board of Registered Electroencephalographic Technologists). Recording electrodes are applied to the scalp using an electrode cap (ElectroCap, Inc., Eaton OH); electrodes are arrayed to record electrical activity from all major brain regions using a standard extension of the International 10-20 system (figure 1). Recording electrodes are connected to an isolation amplifier that is part of the digital EEG system (NuAmp System, NeuroScan, Inc., El Paso, TX). Data are recorded in real-time on computer disk. During recording, subjects will be resting in a quiet room with subdued lighting, in the eyes-closed, maximally alert state; the EEG technologists will alert the subjects whenever drowsiness is evident on the computer monitor. Data will be displayed in real-time on a computer monitor during recording, with adjustable filtering and amplification to facilitate identification of EEG patterns as well as artifact. Data will be collected using a bandpass filter of 0.3 to 70 Hz, and will be digitized at a rate of 250 samples/channel/second. Data will be recorded with a Pz referential montage, and the NeuroScan software then will reformat the data into bipolar montages as needed for the cordance calculations. Three EOG leads will be used (RIO-A2, ROC-A2, and LOC-A1) so that lateral, horizontal, or oblique eye movement artifact may be detected easily. Data for quantitative analysis will be selected from the data recorded according to standard procedures: each EEG will be reviewed by a technician and the first 20-32 seconds of artifact-free data will be selected to be processed to obtain absolute and relative power in four frequency bands (0.5-4 Hz, 4-8 Hz, 8-12 Hz, and 12-20 Hz) after the selections are confirmed by a second technician; both technicians will be blinded to clinical status while making or reviewing the selections.

Two QEEG measures will be calculated for each subject. The first of these is cordance, which will be calculated using an algorithm that has been detailed elsewhere (Leuchter et al., 1999). Cordance is based upon a normalization of absolute and relative power values across all electrode sites and all frequency bands for a given recording. Cordance values have a stronger association with cerebral perfusion in brain tissue underlying each electrode site than do standard QEEG power measures. The second QEEG measure to be examined is QEEG coherence (Leuchter et al., 1992; 1994b), a measure of the shared functional activity between brain regions. Coherence values range between 0 - 1 and are analogous to a correlation coefficient, with values near 1 signifying highly coordinated cerebral activity. Coherence reflects not only cortical activity, but also the function of deep gray matter structures that coordinate cortical activity as well as white-matter tracts connecting brain regions.

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Study Type : Observational
Actual Enrollment : 42 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Examination of Quantitative Electroencephalographic Biomarkers in Huntington's Disease: A Pilot Project
Study Start Date : September 2006
Actual Primary Completion Date : February 2008
Actual Study Completion Date : February 2008

Resource links provided by the National Library of Medicine

Subjects with mild or moderate Huntington's Disease
Normal Controls

Primary Outcome Measures :
  1. Quantitative Electroencephalography Absolute Delta Power. [ Time Frame: baseline- one time point ]
    Absolute power in the delta frequency as measured by quantitative electroencephalography

  2. Quantitative Electroencephalography Absolute Alpha Power. [ Time Frame: baseline EEG ]
    Absolute power in the alpha frequency as measured by quantitative electroencephalography

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
30 subjects with mild or moderate Huntington's Disease and 15 healthy normal controls

Inclusion criteria:

  • Subjects affected by HD or those who are at risk for HD by virtue of having a first-degree relative with the illness, methamphetamine abuse or dependence, as well as normal controls, can participate.
  • All subjects will be above the age of 21.
  • Subjects will be recruited from clinical settings, and will also be self-referred.

Exclusion criteria:

  • Individuals with pacemakers, infusion pumps, or metallic shrapnel will be excluded from MRI assessments.
  • Such implanted metals may be attracted by the MRI machine and put the individual at risk.
  • Moreover, individuals with a history of brain surgery and/or skull fracture will also be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00670709

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United States, California
UCLA Laboratory of Brain, Behavior,a nd PHarmacology
Los Angeles, California, United States, 90024
Sponsors and Collaborators
University of California, Los Angeles
High Q Foundation
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Principal Investigator: Andrew F Leuchter, MD University of California, Los Angeles

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Responsible Party: Andrew F. Leuchter, Andrew F. Leuchter, M.D., University of California, Los Angeles Identifier: NCT00670709     History of Changes
Other Study ID Numbers: QEEG and HD
First Posted: May 2, 2008    Key Record Dates
Results First Posted: August 16, 2010
Last Update Posted: February 11, 2013
Last Verified: February 2013

Keywords provided by Andrew F. Leuchter, University of California, Los Angeles:

Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders