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Essential TremorRULETNCT04576676

Environmental Epidemiology of Essential Tremor

An observational study of Essential Tremor and Parkinson Disease, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for
Essential Tremor, Parkinson Disease
How many people
1,497 participants
Where
1 siteUnited States
Study dates
2 Jul 2020to 19 Jul 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Individuals above the age of 50, living within a 3 hour driving radius of UT Southwestern.

Who may be able to join

  • 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.
Show all 17Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas Southwestern

    Dallas, Texas, 75235

Other trials in United States

About this study

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.

Read the 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.

Medical subject headings
Essential Tremor, Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04576676
Study groupRoleWhat they receive
Essential Tremor1. 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 Disease1. 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 Individuals1. 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 Disease1. 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Level of Harmane in Blood

    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.

    Measured: Day 1

  2. Archimedes Spirals

    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.

    Measured: Day 1

  3. Video Interview

    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.

    Measured: Day 1

Secondary outcomes (14)

  1. Cumulative Illness Rating Scale (CIRS)

    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).

    Measured: Day 1

  2. Montreal Cognitive Assessment (MoCA)

    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.

    Measured: Day 1

  3. Food Frequency Questionnaire

    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.

    Measured: Day 1

  4. Meat Questionnaire

    Asks participants to indicate how often they eat chicken, beef and pork products, and how well done the meats were cooked.

    Measured: Day 1

  5. MDS-Unified Parkinson's Disease Rating Scale

    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.

    Measured: Day 1

  6. Apathy Evaluation Scale (AES)

    The Apathy Evaluation Scale (AES) is a method for measuring apathy resulting from brain-related pathology.

    Measured: Day 1

  7. Beck's Depression Inventory

    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.

    Measured: Day 1

  8. Epworth Sleepiness Scale

    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'.

    Measured: Day 1

  9. Hamilton Anxiety Rating Scale (HAM-A)

    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.

    Measured: Day 1

  10. Patient Health Questionnaire-9

    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.

    Measured: Day 1

  11. Pittsburgh Sleep Quality Index

    PSQI was designed to evaluate overall sleep quality. A total score of "5" or greater is indicative of poor sleep quality.

    Measured: Day 1

  12. The Snaith-Hamilton Pleasure Scale (SHAPS)

    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.

    Measured: Day 1

  13. Tremor Disability Questionnaire

    Assesses a valid index of tremor-induced disability

    Measured: Day 1

  14. Tremor Embarrassment Assessment (TEA)

    TEA is a tool to quantitatively assess the level of embarrassment experienced due to one's tremor.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2020
  2. Study start2 Jul 2020
  3. Primary completion20 Dec 2022
  4. Study completion19 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
1,497 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04576676
Sponsor's protocol ID
STU-2020-0563
Other IDs
R01NS094607
Acronym
RULET
Status last verified
Sep 2023
First submitted
29 Sep 2020
Last updated
21 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Louis ED. Clinical practice. Essential tremor. N Engl J Med. 2001 Sep 20;345(12):887-91. doi: 10.1056/NEJMcp010928. No abstract available.

    PubMed 11565522

  • Louis ED, Applegate LM, Factor-Litvak P, Parides MK, Andrews L. Essential tremor: occupational exposures to manganese and organic solvents. Neurology. 2004 Dec 14;63(11):2162-4. doi: 10.1212/01.wnl.0000145600.91491.f2.

    PubMed 15596771

  • 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.

    PubMed 22981972

  • Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P. Blood harmane concentrations and dietary protein consumption in essential tremor. Neurology. 2005 Aug 9;65(3):391-6. doi: 10.1212/01.wnl.0000172352.88359.2d.

    PubMed 16087903

  • Bhalsing KS, Saini J, Pal PK. Understanding the pathophysiology of essential tremor through advanced neuroimaging: a review. J Neurol Sci. 2013 Dec 15;335(1-2):9-13. doi: 10.1016/j.jns.2013.09.003. Epub 2013 Sep 10.

    PubMed 24060292

  • Benito-Leon J, Louis ED, Bermejo-Pareja F; Neurological Disorders in Central Spain Study Group. Risk of incident Parkinson's disease and parkinsonism in essential tremor: a population based study. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):423-5. doi: 10.1136/jnnp.2008.147223.

    PubMed 19289477

  • Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord. 2010 Apr 15;25(5):534-41. doi: 10.1002/mds.22838.

    PubMed 20175185

  • Bain PG, Findley LJ, Thompson PD, Gresty MA, Rothwell JC, Harding AE, Marsden CD. A study of hereditary essential tremor. Brain. 1994 Aug;117 ( Pt 4):805-24. doi: 10.1093/brain/117.4.805.

    PubMed 7922467

  • Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F; Neurological Disorders in Central Spain (NEDICES) Study Group. A population-based study of mortality in essential tremor. Neurology. 2007 Nov 20;69(21):1982-9. doi: 10.1212/01.wnl.0000279339.87987.d7.

    PubMed 18025392

  • Fekete R, Jankovic J. Revisiting the relationship between essential tremor and Parkinson's disease. Mov Disord. 2011 Feb 15;26(3):391-8. doi: 10.1002/mds.23512.

    PubMed 21462256

  • MARSHALL J. Observations on essential tremor. J Neurol Neurosurg Psychiatry. 1962 May;25(2):122-5. doi: 10.1136/jnnp.25.2.122. No abstract available.

    PubMed 14470250

  • Louis ED, Vonsattel JP, Honig LS, Lawton A, Moskowitz C, Ford B, Frucht S. Essential tremor associated with pathologic changes in the cerebellum. Arch Neurol. 2006 Aug;63(8):1189-93. doi: 10.1001/archneur.63.8.1189.

    PubMed 16908751

  • Moncrieff J. Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection. J Chromatogr. 1989 Nov 24;496(2):269-78. doi: 10.1016/s0378-4347(00)82576-1.

    PubMed 2613832

  • Skog K, Solyakov A, Arvidsson P, Jagerstad M. Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectrometry. J Chromatogr A. 1998 Apr 17;803(1-2):227-33. doi: 10.1016/s0021-9673(97)01266-1.

    PubMed 9604333

  • Gironell A, Kulisevsky J, Barbanoj M, Lopez-Villegas D, Hernandez G, Pascual-Sedano B. A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor. Arch Neurol. 1999 Apr;56(4):475-80. doi: 10.1001/archneur.56.4.475.

    PubMed 10199338

Questions about this trial

What is this clinical trial studying?

An observational study of Essential Tremor and Parkinson Disease, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Level of Harmane in Blood (time frame: Day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04576676, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.

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