Natural History Study of Synucleinopathies

Conditions

• Dementia With Lewy Bodies
• Multiple System Atrophy
• Neurogenic Orthostatic Hypotension
• Parkinson Disease
• Patients With Synucleinopathies
• Pure Autonomic Failure
• REM Sleep Behavior Disorder
• Shy-Drager Disease

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Study Details

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 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.

Key Dates

Start date

Jun 30, 2011

Status verified

Jun 2026

Primary completion

Dec 30, 2026

Completion

Dec 30, 2026

Study Design

Enrollment

800 participants (estimated)

Arms

• Arm: REM sleep behavior disorder, RBD
  Patients that have rapid eye movement sleep behavior disorder.
• Arm: multiple system atrophy
  is a neurodegenerative disorder charaterized by abnormal alpha-synuclein deposition in the cytoplasm of oligodendroglial cells in the CNS, and typically sparing peripheral autonomic nerves.
• Arm: Pure Autonomic failure
  A neurodegenerative disorder characterized by loss of peripheral noradrenergic fibers, with low levels of plasma norepinephine.
• Arm: Parkinson disease
  A degenerative disorder of the central nervous system that leads to termors, difficulty walking, movement and coordination.
• Arm: Dementia with Lewy bodies
  A neurodegenerative disorder similar to PAF and PD with the accumulation of Alpha-synuclein in the CNS however DLB patients develop dementia.

Primary Outcome Measure

To create a database of primary autonomic disorders that will serve as a phenotyping core. [ Time Frame: 5 years ]

Central Contacts

• Horacio Kaufmann, MD
  212-263-7225
  [email protected]
• Grace Nkrumah
  212-263-7225
  [email protected]

Locations (5)

Find similar trials in Boston, MA

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