Hereditary Parkinson s Disease Natural History Protocol

NCT ID: NCT02511015

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 31 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-07-08
• Study Completion Date: 2017-08-15

Brief Summary

Background:

• Parkinson s disease is a disease of the nervous system that affects movement. People usually get it in their 70s or 80s. Early onset Parkinson s disease (EOPD) begins before the age of 50. Researchers think EOPD may be caused by a mutation in a gene. They want to study the genetic causes so they can find therapies for this disease.

Objective:

• To better understand the genetic causes of EOPD.

Eligibility:

• Adults ages 18 80 with a history of EOPD. Their family members, who do not have Parkinson s disease, can join as controls.
• Healthy volunteers ages 18 80.

Design:

• Participants with EOPD and their relatives will be screened with a review of medical records. Healthy volunteers will have medical history, physical exam, and blood drawn.
• Relatives may send blood samples to NIH to test for mutations in genes that are linked to Parkinson s disease. They may have a physical exam.
• Participants may be asked to return to clinic for another visit that can last up to 2 hours.
• During this visit, participants will have blood taken from a vein in the arm via a needle stick.
• Participants may give a sample of their skin. The skin on the arm or leg will be numbed and a small skin punch biopsy will be taken with a special needle.
• Some cells from the blood or skin sample may be grown in a lab to establish cell lines. The cells may also potentially be genetically modified to make stem cells.
• Researchers may perform genetic analysis on the samples to compare them to EOPD patient samples.

Detailed Description

The majority of subjects with the degenerative Parkinson's Disease (PD) present in the 7th and 8th decades of life. In contrast, this neurologic disease can present within the first 5 decades of life. This early onset presentation is more likely to have a direct genetic cause relative to the etiology of the degenerative form of the disease. Our understanding of the genetic causes of early onset Parkinson's Disease (EOPD) may help us find therapies for both the genetic and degenerative illnesses. Data from our laboratory and others show that genetic mutations associated with EOPD, disrupt cellular stress-response programs. These perturbations, in turn, impair cell-repair process, which is hypothesized to increase susceptibility to dopaminergic neuron degeneration linked to EOPD and degenerative PD. At the same time, patients with EOPD have a variable age of onset (spanning from 8 years to 41 years in the subjects in our cohort) and disease penetrance (severity of symptoms). The hypothesis we propose to test is whether the number and allele distributions of EOPD susceptibility gene mutations account for the variable age of onset and disease penetrance. This hypothesis will be tested in this natural history protocol by genotyping subjects with EOPD to define their genetic defects and to explore the cellular reparative function in these individuals using peripheral blood cells, skin biopsy derived fibroblasts and induced pluripotential stems cells derived from these subjects. In parallel, the phenotype of these subjects will be evaluated by the NINDS Parkinson's Clinic. Together, these data should advance our insight into the genotype-phenotype in EOPD pathophysiology.

Conditions

Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Family Member Control Subjects

Family members, of enrolled EOPD subjects, who themselves do not have Parkinson disease or Parkinsonism can be enrolled as controls on this study.

No interventions assigned to this group

Healthy Control Subjects

Age 18 years to 80 years old with no history or family history of Parkinson disease or Parkinsonism.

No interventions assigned to this group

Parkinson Subjects

Age 18 years to 80 years old with a history of early onset Parkinson disease or Parkinsonism (Presentation within the first five decades of life).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Parkinson's Subjects

• Age 18 years to 80 years old with a history of early onset Parkinson's disease or Parkinsonism (Presentation within the first five decades of life).

Healthy Control Subjects

• Age 18 years to 80 years old with no history or family history of Parkinson's disease or Parkinsonism.

Family Member Control Subjects

-Family members, of enrolled EOPD subjects, who themselves do not have Parkinson's disease or Parkinsonism can be enrolled as controls on this study.

All Subjects

• Willingness and legal ability to give and sign informed study consent
• Willingness to have blood or tissue samples studied, and potentially stored for future research

Exclusion Criteria

All Subjects

• Subjects who are unable or unwilling to sign an informed consent
• Subjects with genetic defects associated with diseases including other neurologic syndromes.
• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek P Narendra, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE. Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol. 2007 Jul;6(7):652-62. doi: 10.1016/S1474-4422(07)70174-6.

Reference Type: BACKGROUND

PMID: 17582365 (View on PubMed)

Greenamyre JT, Hastings TG. Biomedicine. Parkinson's--divergent causes, convergent mechanisms. Science. 2004 May 21;304(5674):1120-2. doi: 10.1126/science.1098966. No abstract available.

Reference Type: BACKGROUND

PMID: 15155938 (View on PubMed)

Arbuthnott GW, Wickens J. Space, time and dopamine. Trends Neurosci. 2007 Feb;30(2):62-9. doi: 10.1016/j.tins.2006.12.003. Epub 2006 Dec 13.

Reference Type: BACKGROUND

PMID: 17173981 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-H-0155.html

NIH Clinical Center Detailed Web Page

Other Identifiers

15-H-0155

Identifier Type: -

Identifier Source: secondary_id

150155

Identifier Type: -

Identifier Source: org_study_id