6106: Natural History Study of Synucleinopathies

Status: Recruiting

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.

For Diseases:

  • Pure autonomic failure
  • Multiple system atrophy
  • Dementia with Lewy bodies
  • Parkinson disease
  • Disorders associated with orthostatic hypotension in which the underlying cause is unclear

Background

Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA).
 
However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain.

After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson's disease.

The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA – the most aggressive of the synucleinopathies.

At each visit you will be asked to:

  • Give details about your medical problems
  • Have a physical examination
  • Have a neurological exam with an assessment of your cognitive skills
  • Fill out questionnaires about your symptoms, sleep problems and life
  • Have an electrocardiogram
  • Give blood (4 teaspoons)
  • Give a sample of urine
  • Undergo a series of standardized autonomic tests in which your blood pressure and heart rate are recorded while laying flat, standing upright on a tilt table and during different breathing exercises.
  • Recognize smells

We will also look at your medical records so that we can collect information about your medical history, problems you may have during sleep and the structure of your heart.

The number of office visits you will be asked to attend will depend on your diagnosis. If you have orthostatic hypotension and problems with movement, you will not need to come in for annual office visits and we will follow you by phone instead. Your doctor will provide you with details as to your level of participation.

Targeted Enrollment

To be eligible to participate, you must:

  • Referred to any of the participating consortium sites with any of the following conditions:
    1. Neurogenic orthostatic hypotension defined as 20 mmHg fall in systolic BP or 10 mmHg fall in diastolic BP when upright,  also including post prandial hypotension, exercise-induced hypotension and delayed orthostatic hypotension. OR
    2. Probable or possible multiple system atrophy defined by consensus criteria OR
    3. Parkinson's disease/dementia with Lewy bodies OR
    4. REM sleep behavior disorder.
  • Be aged 18 or over

You are not eligible to participate if:

For Participants with PAF:

  • Exaggerated tachycardia on orthostasis that in the investigators opinion indicates intact cardiovascular autonomic reflexes
  • Drug-induced orthostatic hypotension (i.e., the use of alpha-blockers, diuretics, tricyclic antidepressants or others thought by the investigator to be the main reason for the patient's orthostatic hypotension)
  • Isolated vasovagal syncope
  • Systemic illness thought to be responsible for the orthostatic hypotension including but not limited to congestive heart failure, lupus, collagen/vascular disease or diabetes

For All Participants:

  • Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study.
  • Concurrent (other) neurologic conditions like stroke, or systemic disorders (poorly controlled diabetes or severe B12 deficiency) that in the opinion of the investigator may affect the interpretation of the studies

How to participate

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation

United States

California

  • Stanford University, Palo Alto
    Department of Neurology
    Contact: Mitchell Miglis, MD
    Principal Investigator 
    650-723-6469
    mmiglis@stanford.edu

Massachusetts

  • Beth Israel Deaconess Medical Center, Boston
    Center for Autonomic and Peripheral Nerve Disorders
    Contact: Sharika Rajan
    Research Coordinator 
    617-632-0864
    srajan@bidmc.harvard.edu
     
  • Massachusetts General Hospital / Harvard University, Boston
    Department of Neurology
    Contact: Jason MacMore
    SeniorCoordinator 
    617-726-5060
    jmacmore@mgh.harvard.edu

Michigan

  • University of Michigan, Ann Arbor
    Closed to Accrual
    Contact: Arijit Bhaumik, BA
    Sr. Clinical Research Coordinator
    734-936-8281
    arijit@umich.edu

Minnesota

New York

Tennessee

Texas

International

Argentina

Austria

Italy

  • University of Salerno, Salerno
    Contact: Dr. Maria Teresa Pellecchia
    Principal Investigator
    +39 089 96 9121
    mpellecchia@unisa.it

South Korea

Spain

  • Hospital Clinic de Barcelona, Barcelona
    Contact: Mònica Serradell, BSc
    +34 93 227 54 13
    narcolps@clinic.ub.es
     
  • Hospital Clinic de Barcelona, Movement Disorders, Barcelona
    Contact: Pilar Santacruze, PhD
    +34 93 227 57 85
    PSANTA@clinic.cat
     
  • Hospital Universitari Mútua de Terrassa, Terrassa
    Contact: Judit Lopez
    +34 93 736 50 50 ext. 12787
    neurologia@mutuaterrassa.es

 

Stay Connected - Join the Contact Regsitry

The RDCRN Autonomic Disorders Consortium Contact Registry is a way for patients with rare diseases and their family members to learn about research studies they may be able to join.

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