Clinical trial NCT04576676: Environmental Epidemiology of Essential Tremor
Official title: Environmental Epidemiology of Essential Tremor
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Essential Tremor
Parkinson Disease
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Purdue University
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Yale University
First posted: 2020-10-06
Enrollment: 1497
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals above the age of 50, living within a 3 hour driving radius of UT Southwestern.

Brief 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), the investigator's goal is to nail down the links between HA and ET and to further solidify the emerging links between HA and PD.

Detailed description: This research is devoted to studying the causes of tremor, and especially essential tremor (ET), which is the most common type of tremor. Since 2000, this lab has 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, the investigators 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, the investigators 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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
* 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
* 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

Exclusion Criteria:

* Healthy Individuals

  * Subjects with medical history of neurological conditions
  * Subjects with family history of neurological condition
  * Subjects with spouse diagnosed with Essential Tremor or Parkinson's Disease
* Essential Tremor

  * Subjects with medical history of another movement disorder such as Parkinson's Disease or dystonia
  * Subjects with head tremor that preceded hand tremor
* Parkinson's Disease

  --Subjects with medical history of Essential Tremor
* Essential Tremor and Parkinson's Disease

  * Criteria that does not meet inclusion

Primary outcomes:
measure: Level of Harmane in Blood
timeFrame: Day 1
measure: Archimedes Spirals
timeFrame: Day 1
measure: Video Interview
timeFrame: Day 1
Secondary outcomes:
measure: Cumulative Illness Rating Scale (CIRS)
timeFrame: Day 1
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Day 1
measure: Food Frequency Questionnaire
timeFrame: Day 1
measure: Meat Questionnaire
timeFrame: Day 1
measure: MDS-Unified Parkinson's Disease Rating Scale
timeFrame: Day 1
measure: Apathy Evaluation Scale (AES)
timeFrame: Day 1
measure: Beck's Depression Inventory
timeFrame: Day 1
measure: Epworth Sleepiness Scale
timeFrame: Day 1
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Day 1
measure: Patient Health Questionnaire-9
timeFrame: Day 1
measure: Pittsburgh Sleep Quality Index
timeFrame: Day 1
measure: The Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Day 1
measure: Tremor Disability Questionnaire
timeFrame: Day 1
measure: Tremor Embarrassment Assessment (TEA)
timeFrame: Day 1
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: UTSW Medical Center
name: Nora C Hernandez, M.D.
role: STUDY_DIRECTOR
affiliation: UTSW Medical Center
name: Allison Powell, BA
role: STUDY_DIRECTOR
References:
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citation: Louis ED, Benito-Leon J, Moreno-Garcia S, Vega S, Romero JP, Bermejo-Pareja F, Gerbin M, Viner AS, Factor-Litvak P, Jiang W, Zheng W. Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor cases in Spain. Neurotoxicology. 2013 Jan;34:264-8. doi: 10.1016/j.neuro.2012.09.004. Epub 2012 Sep 12.
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