Systemic Synuclein Sampling Study (S4)

NCT02572713 | Completed

• 1 other identifier: S4-001
• Study Type: observational
• Target: 80
• Locations: 2 countries
• Sites: 6

Brief Summary

The purpose of this study is to measure alpha-synuclein in peripheral body tissues and fluids in Parkinson's disease (PD). This may help in developing better treatments for PD patients in the future.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; alpha-synuclein; biomarker

Outcome Measures

Primary Outcomes (6)

• α-syn levels in blood

  Blood will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  24 months

• α-syn levels in saliva

  Saliva will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  24 months

• α-syn levels in CSF

  CSF will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  24 months

• α-syn deposits in skin

  α-syn burden in skin biopsies will be expressed as 1) simply positive or negative, i.e. whether any two slides are positive out of all examined 2) by total percentage of slides examined that are positive 3) by site of highest density of positive α-syn fibers.

  24 months

• α-syn deposits in submandibular gland

  α-syn burden in the submandibular tissue will be expressed as 1) simply positive or negative, i.e. whether any two slides are positive out of all examined 2) by total percentage of slides examined that are positive 3) by site of highest density of positive α-syn fibers.

  24 months

• α-syn deposits in colon

  α-syn burden in the colon tissue will be expressed as 1) simply positive or negative, i.e. whether any two slides are positive out of all examined 2) by total percentage of slides examined that are positive 3) by site of highest density of positive α-syn fibers.

  24 months

Study Arms (4)

Early PD

20 early PD not requiring dopamine replacement therapy have been enrolled.

Procedure: Biofluid samplings; Procedure: Tissue samplings; Drug: DaTSCAN™

Moderate PD

20 moderate PD on dopamine replacement therapy without motor fluctuations have been enrolled.

Procedure: Biofluid samplings; Procedure: Tissue samplings; Drug: DaTSCAN™

Advanced PD

21 advanced PD with motor fluctuations have been enrolled.

Procedure: Biofluid samplings; Procedure: Tissue samplings; Drug: DaTSCAN™

Healthy Controls

21 healthy controls have been enrolled.

Procedure: Biofluid samplings; Procedure: Tissue samplings; Drug: DaTSCAN™

Interventions

Biofluid samplings PROCEDURE

Biofluid samplings (blood, saliva, and cerebrospinal fluid (CSF)

Advanced PD; Early PD; Healthy Controls; Moderate PD

Tissue samplings PROCEDURE

Tissue samplings (skin, colon, submandibular gland)

Advanced PD; Early PD; Healthy Controls; Moderate PD

DaTSCAN™ DRUG

Also known as: ioflupane-123I

Advanced PD; Early PD; Healthy Controls; Moderate PD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited through patient care clinics, physician referrals, and by reaching out to the community (e.g. PD-affiliated groups).

You may qualify if:

• Male or female age 40 or older at the time of PD diagnosis.
• Clinical diagnosis of PD based on bradykinesia plus one of the following: rest tremor or rigidity.
• DAT deficit at screening based on visual interpretation of DaTSCAN™ imaging.
• PD subjects will need to fall into one of the following stages:
• Early untreated PD not requiring dopamine replacement medication (anticholinergics, MAO-B inhibitors and amantadine permitted), Hoehn and Yahr 1-2, \< 2 years from diagnosis.
• Moderate PD responsive and currently treated with dopamine replacement therapy without evidence of motor fluctuations or dyskinesias.
• Advanced PD with motor fluctuations or dyskinesias, \> 5 years from diagnosis.
• Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations.
• Willing and able to comply with scheduled visits, required study procedures and laboratory tests.
• Male or female age 50 or older at the time of the screening visit
• Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations.
• Willing and able to comply with scheduled visits, required study procedures and laboratory tests.

You may not qualify if:

• Has a history of cancer (other than basal and squamous cell skin cancers), autoimmune disorder, liver disease, or other hematological disorder within the past 5 years.
• Current treatment with anticoagulants (e.g., Coumadin, heparin) that would preclude safe completion of the lumbar puncture (LP) and tissue biopsy procedures.
• Current treatment with an antiplatelet agent (Plavix or aspirin \>325 mg/day).
• Has a diagnosis of diabetes mellitus requiring either an oral agent or insulin therapy.
• A bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
• Has received botulinum toxin injections to the submandibular gland within the past year.
• Has a condition that precludes safe performance of routine LP, such as prohibitive lumbar spinal disease.
• Has a condition that precludes the safe performance of the flexible sigmoidoscopy procedure or may interfere with obtaining evaluable colonic tissue biopsies, including a prior colonoscopy with significant findings (e.g. polyp with a positive finding, ulcerative colitis, Crohn's disease, inflammatory disease).
• Has a condition that precludes the safe performance of the submandibular gland procedure or may interfere with obtaining evaluable submandibular tissue biopsies, including any previous or active significant disease affecting the submandibular gland (e.g. inflammatory disease, infection, tumor).
• Has a condition that precludes the safe performance of the skin punch biopsy procedure or may interfere with obtaining evaluable skin tissue biopsies, including any previous or active significant dermatological disease (e.g. previous biopsy with any of the following findings: inflammatory disease, scar tissue, psoriasis, keloid formation, skin cancer).
• Any other medical or psychiatric condition or laboratory abnormality, which in the opinion of the Site Investigator would preclude participation.
• Use of investigational drugs or devices within 30 days prior to the screening visit.
• Has other significant neurological disorders (clinically significant stroke, brain tumor, hydrocephalus, epilepsy, other neurodegenerative disorders, encephalitis, repeated head trauma, polyneuropathy).
• Has significant autonomic dysfunction (symptomatic orthostasis, hypotension or urinary incontinence) suggestive of an atypical parkinsonism.
• Has atypical features of parkinsonism including but not limited to supranuclear gaze palsy, early recurrent falls, corticospinal track abnormalities, cerebellar abnormalities, significant cognitive dysfunction.

Sponsors & Collaborators

• Michael J. Fox Foundation for Parkinson's Research: lead
• Indiana University: collaborator
• University of Iowa: collaborator
• Banner Health: collaborator
• Paracelsus Elena Klinik: collaborator

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Institute for Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Toronto Western Hospital Movement Disorders Centre

Toronto, Ontario, M5T 2S8, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biofluid samplings \[blood, saliva, and cerebrospinal fluid (CSF)\] Tissue samplings (skin, colon, submandibular gland)

MeSH Terms

Conditions

Parkinson Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

ioflupane

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Lana Chahine, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Co-PI

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 9, 2015
• Study Start: October 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 17, 2017

Record last verified: 2017-08

Locations

US (5); CA (1)