Environmental Epidemiology of Essential Tremor

Study First Received, September 29,2020
Lead Sponsor: University of Texas Southwestern Medical Center (Funder Type: Other)
Conditions
Essential Tremor, Parkinson Disease
Study Type
Observational
Status
ongoing, recruiting (500 patients)
Study Duration
2020-07-02 to 05/2022
Overview Outcomes Eligibility Locations Investigators No Results
Overview
Official Title
Environmental Epidemiology of Essential Tremor

Acronym
RULET

Summary
This study's research is devoted to studying the causes of tremor, and especially essential tremor (ET), which is the most common type of tremor. Previous studies have revealed a link between harmane [HA], a dietary neurotoxin, and ET; these studies now also suggest a link between this toxin and Parkinson's disease (PD), a related tremor disorder. Yet these links are tentative rather than conclusively established; therefore, in this new patient-based proposal, which incorporates investigations spanning two continents (North America and Europe), utilizes several complementary study designs (prospective cohort, case control), and draws on several types of tissue (blood, brain), our goal is to nail down the links between HA and ET and to further solidify the emerging links between HA and PD.

Detailed Description
Our research is devoted to studying the causes of tremor, and especially essential tremor (ET), which is the most common type of tremor. Since 2000, we have been investigating whether several environmental neurotoxins are associated with ET. A link between harmane (HA) (1-methyl-9H-pyrido[3,4-b]indole) and ET has been emerging from these studies, which show that blood and brain HA concentration ([HA]) is elevated in ET cases (esp. familial ET) vs. control subjects. HA is a neurotoxin present in the diet (esp. in meat). Administration of HA to laboratory animals produces severe action tremor resembling ET. Yet the link between HA and ET has not been convincingly established. All epidemiological studies have been case-control studies; thus, it is not clear whether high blood [HA] precedes the onset of ET. Aim 1 of this proposal will address this issue. The HA story has also become more complex and multi-dimensional. Thus, we were recently intrigued to find that blood [HA] was higher in Parkinson's disease (PD) cases than controls in New York. HA is structurally similar to MPTP, a neurotoxin closely linked with PD. ET and PD are both tremor disorders; some patients develop both disorders (ET+PD; i.e., they are comorbid for the two conditions). Whether the HA - PD link is reproducible, whether it tracks with the subtype of PD in which tremor rather than bradykinesia/rigidity is the predominant feature, and whether biomarker findings from blood also occur in the target organ of interest (i.e., the brain) in PD is not known. Aim 2 of this proposal will address this myriad of issues. Finally, whether individuals who are comorbid for both ET and PD have the highest blood [HA] is not known. Aim 3 of this proposal will address this issue. To close these gaps in knowledge, in this application, we propose a 5-year study with 3 inter-related aims that draw on several types of human tissue (blood, brain): AIM 1: To nail down the links between HA and ET by studying the association between baseline blood [HA] and the development of incident ET in a cohort study. AIM 2: To further solidify the emerging links between HA and PD by extending our observations to another country (Spain). AIM 3: To assess blood levels of HA in patients who have both ET and PD (ET+PD). This would be the only study heading in this direction - exploring the etiological role of environmental factors, and more specifically toxins, in ET. It would thus complement the many ongoing studies searching for ET genes. The study could lead to the clear identification of the first modifiable risk factor for ET (i.e., dietary HA).This would also be the only study assessing the possible etiological role and tissue concentrations of this toxin, HA, which is structurally similar to MPTP, in patients with PD.

Arms
Essential Tremor Subjects must be 50 years of age or older. Subjects must have been diagnosed with Essential Tremor Subjects must live within 3 hours of UTSW Subjects will be screened for eligibility over the phone, and if eligible, will partake in a virtual video conference with a research assistant. Subjects will also travel to the Aston Building at UTSW for a blood draw.
Parkinson's Disease Subjects must be 50 years of age or older. Subjects must have been diagnosed with Parkinson's Disease Subjects must live within 3 hours of UTSW Subjects will be screened for eligibility over the phone, and if eligible, will partake in a virtual video conference with a research assistant. Subjects will also travel to the Aston Building at UTSW for a blood draw.
Healthy Individuals Healthy individuals living within 3 hours of UTSW Subjects must be 50 years of age or older You are healthy and have not being diagnosed with any neurological disease Subjects will be screened for eligibility over the phone, and if eligible, will partake in a virtual video conference with a research assistant. Subjects will also travel to the Aston Building at UTSW for a blood draw.
Essential Tremor and Parkinson's Disease Subjects must be 50 years of age or older. Subjects must have been diagnosed with Essential Tremor Subjects must have been diagnosed with Parkinson's Disease preceded by at least 3 years of enrollment in study Subjects must live within 3 hours of UTSW Subjects will be screened for eligibility over the phone, and if eligible, will partake in a virtual video conference with a research assistant. Subjects will also travel to the Aston Building at UTSW for a blood draw.

Funder Type
Other

Lead Sponsor
University of Texas Southwestern Medical Center

Collaborators
Purdue University (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Yale University (Other)

First Received
2020-09-29

Last Updated
2020-09-29

Start Date
2020-07-02

Primary Completion
05/2021

Completion Date
05/2022

NCT Identifie
NCT04576676

Identifiers
R01NS094607 NCT04576676

Contact Information
Elan Louis, M.D., M.S., 214-648-3751, elan.louis@utsouthwestern.edu

Outcomes
Eligibility
Locations
Investigators
No Results