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Environmental Epidemiology of Essential Tremor (RULET)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04576676
Recruitment Status : Recruiting
First Posted : October 6, 2020
Last Update Posted : August 31, 2022
Sponsor:
Collaborators:
Purdue University
National Institute of Neurological Disorders and Stroke (NINDS)
Yale University
Information provided by (Responsible Party):
Elan Louis, University of Texas Southwestern Medical Center

Study Description
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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.

Condition or disease
Essential Tremor Parkinson Disease

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.
Study Design
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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Environmental Epidemiology of Essential Tremor
Actual Study Start Date : July 2, 2020
Estimated Primary Completion Date : April 19, 2023
Estimated Study Completion Date : April 19, 2023

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
Essential Tremor
  1. Subjects must be 50 years of age or older.
  2. Subjects must have been diagnosed with Essential Tremor
  3. 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
  1. Subjects must be 50 years of age or older.
  2. Subjects must have been diagnosed with Parkinson's Disease
  3. 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
  1. Healthy individuals living within 3 hours of UTSW
  2. Subjects must be 50 years of age or older
  3. 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
  1. Subjects must be 50 years of age or older.
  2. Subjects must have been diagnosed with Essential Tremor
  3. Subjects must have been diagnosed with Parkinson's Disease preceded by at least 3 years of enrollment in study
  4. 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.


Outcome Measures
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Primary Outcome Measures :
  1. Level of Harmane in Blood [ Time Frame: Day 1 ]
    Two vials of veinous blood will be collected from each participant and analyzed for the level of harmane. Specimen collection done at the Aston Care Center and sent to Purdue University for analysis.

  2. Archimedes Spirals [ Time Frame: Day 1 ]
    Each participant will draw two spirals with each hand, used to assess the frequency and severity of one's tremor and to confirm their diagnosis.

  3. Video Interview [ Time Frame: Day 1 ]
    After a participant has met the eligibility criteria, they participate in a two hour video interview, where a series of questionnaires is administered, as well as a videotaped neurological/movement assessment. Video is reviewed by study's PI and participant's tremor is rated on a fixed, numerical scale from 0.0 to 4.0, where 4.0 indicates a more severe tremor.


Secondary Outcome Measures :
  1. Cumulative Illness Rating Scale (CIRS) [ Time Frame: Day 1 ]
    CIRS quantifies the burden of disease in elderly patients (comorbidity scale; ranges from 0-42 where 42 indicates highest number and severity of illnesses measured).

  2. Montreal Cognitive Assessment (MoCA) [ Time Frame: Day 1 ]
    The MoCA is a cognitive screening test designed to assist Health Professionals in the detection of mild cognitive impairment and Alzheimer's disease. Scores range from 0-30.

  3. Food Frequency Questionnaire [ Time Frame: Day 1 ]
    Developed at Harvard University, the Food Frequency Questionnaire (FFQ) is a limited checklist of foods and beverages with a frequency response section for subjects to report how often each item was consumed over a specified period of time.

  4. Meat Questionnaire [ Time Frame: Day 1 ]
    Asks participants to indicate how often they eat chicken, beef and pork products, and how well done the meats were cooked.

  5. MDS-Unified Parkinson's Disease Rating Scale [ Time Frame: Day 1 ]
    The UPDRS scale refers to Unified Parkinson Disease Rating Scale, and it is a rating tool used to gauge the course of Parkinson's disease in patients. Each of the ratings ranges from 0 to 4. The original UPDRS included only integers, but some use 0.5 increments; however, use of these 0.5 increments has not undergone clinimetric testing or validation. The total score for subscale 3 ranges from 0 to 108, the sum of scores from 27 observations.

  6. Apathy Evaluation Scale (AES) [ Time Frame: Day 1 ]
    The Apathy Evaluation Scale (AES) is a method for measuring apathy resulting from brain-related pathology.

  7. Beck's Depression Inventory [ Time Frame: Day 1 ]

    The Beck Depression Inventory (BDI, BDI-1A, BDI-II) is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression.

    Like the BDI, the BDI-II also contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs used differ from the original:

    0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression.


  8. Epworth Sleepiness Scale [ Time Frame: Day 1 ]
    The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.

  9. Hamilton Anxiety Rating Scale (HAM-A) [ Time Frame: Day 1 ]
    The HAM-A was one of the first rating scales developed to measure the severity of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.

  10. Patient Health Questionnaire-9 [ Time Frame: Day 1 ]
    The Patient Health Questionnaire (PHQ)-9 is the major depressive disorder (MDD) module of the full PHQ. Used to provisionally diagnose depression and grade severity of symptoms in general medical and mental health settings.

  11. Pittsburgh Sleep Quality Index [ Time Frame: Day 1 ]
    PSQI was designed to evaluate overall sleep quality. A total score of "5" or greater is indicative of poor sleep quality.

  12. The Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Day 1 ]
    The SHAPS is a 14-item scale that measures anhedonia, the inability to experience pleasure. The items cover the domains of: social interaction, food and drink, sensory experience, and interest/pastimes. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more.

  13. Tremor Disability Questionnaire [ Time Frame: Day 1 ]
    Assesses a valid index of tremor-induced disability

  14. Tremor Embarrassment Assessment (TEA) [ Time Frame: Day 1 ]
    TEA is a tool to quantitatively assess the level of embarrassment experienced due to one's tremor.


Biospecimen Retention:   Samples With DNA
2 vials of veinous blood.

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Individuals above the age of 50, living within a 3 hour driving radius of UT Southwestern.
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
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 ClinicalTrials.gov identifier (NCT number): NCT04576676


Contacts
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Contact: Elan D Louis, M.D., M.S. 214-648-3751 elan.louis@utsouthwestern.edu
Contact: Nora C Hernandez, M.D. 214-648-3485 nora.hernandez@utsouthwestern.edu

Locations
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United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75235
Contact: Nora C Hernandez, M.D.    214-648-3485    nora.hernandez@utsouthwestern.edu   
Contact: Allison Powell, B.A.    214-648-9884    allison.powell@utsouthwestern.edu   
Principal Investigator: Elan D Louis, M.D., M.S.         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Purdue University
National Institute of Neurological Disorders and Stroke (NINDS)
Yale University
Investigators
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Study Director: Nora C Hernandez, M.D. UTSW Medical Center
Study Director: Allison Powell, BA UTSW Medical Center
  Study Documents (Full-Text)

Documents provided by Elan Louis, University of Texas Southwestern Medical Center:
Informed Consent Form  [PDF] August 5, 2022

More Information
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Publications:

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Responsible Party: Elan Louis, Professor and Chairman of Neurology, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04576676    
Other Study ID Numbers: STU-2020-0563
R01NS094607 ( U.S. NIH Grant/Contract )
First Posted: October 6, 2020    Key Record Dates
Last Update Posted: August 31, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

We are committed to making the resources of this study widely available not only to scientists studying ET but to those studying other neurological and neurodegenerative diseases as well, and especially to those who are studying PD. Thus, sharing data generated by this project is an important part of our proposed activities and will be carried out in a number of different ways. Our Data Sharing plan will adhere to the general principles outlined in the NIH Data Sharing Policy and Implementation Guidance.

The aims of the present proposal not only include clinical data but also data from measurement of harmane in blood and brain tissue samples. Data/tissue will be shared for all study participants that have consented to data sharing. Participants who did not give consent for data sharing will be excluded.
Time Frame: Data will become available after the recruitment is complete and the biological samples have been analyzed.
Access Criteria:

The results and conclusions of our analysis will be shared at global scientific meetings and in the scientific literature (during publication in peer-reviewed journals). An additional mechanism of sharing data will be in the form of supplements to the additional data, which, for most journals, is on-line.

The data will be entered into SPSS data files. Original data files for individual runs will be shared with colleagues who possess the means and knowledge to utilize them, under collaborative agreement. To strengthen data confidentiality and safeguard the privacy of study participants, we will make data available to approved researchers under a data-sharing agreement that provides for (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology and (3) a commitment to destroying or returning the data after analyses are completed.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Tremor
Essential Tremor
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Dyskinesias
Neurologic Manifestations