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Systemic Synuclein Sampling Study (S4) (S4)

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ClinicalTrials.gov Identifier: NCT02572713
Recruitment Status : Completed
First Posted : October 9, 2015
Last Update Posted : August 17, 2017
Sponsor:
Collaborators:
Indiana University
University of Iowa
Banner Health
Paracelsus Elena Klinik
Information provided by (Responsible Party):
Lana Chahine, MD, University of Pennsylvania

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.

Condition or disease Intervention/treatment
Parkinson's Disease Procedure: Biofluid samplings Procedure: Tissue samplings Drug: DaTSCAN™

Detailed Description:
This is a multi-center, cross-sectional, observational study to evaluate α-syn pathology in multiple tissues and biofluids in individual subjects with PD and HC at a single time point.

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Study Type : Observational
Actual Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Systemic Synuclein Sampling Study (S4)
Study Start Date : October 2015
Actual Primary Completion Date : August 1, 2017
Actual Study Completion Date : August 1, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Early PD
20 early PD not requiring dopamine replacement therapy have been enrolled.
Procedure: Biofluid samplings
Biofluid samplings (blood, saliva, and cerebrospinal fluid (CSF)

Procedure: Tissue samplings
Tissue samplings (skin, colon, submandibular gland)

Drug: DaTSCAN™
Other Name: ioflupane-123I

Moderate PD
20 moderate PD on dopamine replacement therapy without motor fluctuations have been enrolled.
Procedure: Biofluid samplings
Biofluid samplings (blood, saliva, and cerebrospinal fluid (CSF)

Procedure: Tissue samplings
Tissue samplings (skin, colon, submandibular gland)

Drug: DaTSCAN™
Other Name: ioflupane-123I

Advanced PD
21 advanced PD with motor fluctuations have been enrolled.
Procedure: Biofluid samplings
Biofluid samplings (blood, saliva, and cerebrospinal fluid (CSF)

Procedure: Tissue samplings
Tissue samplings (skin, colon, submandibular gland)

Drug: DaTSCAN™
Other Name: ioflupane-123I

Healthy Controls
21 healthy controls have been enrolled.
Procedure: Biofluid samplings
Biofluid samplings (blood, saliva, and cerebrospinal fluid (CSF)

Procedure: Tissue samplings
Tissue samplings (skin, colon, submandibular gland)

Drug: DaTSCAN™
Other Name: ioflupane-123I




Primary Outcome Measures :
  1. α-syn levels in blood [ Time Frame: 24 months ]
    Blood will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  2. α-syn levels in saliva [ Time Frame: 24 months ]
    Saliva will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  3. α-syn levels in CSF [ Time Frame: 24 months ]
    CSF will be analyzed using the most optimal, currently available, quantitative assays. The outcome will be expressed as a concentration of α-syn levels.

  4. α-syn deposits in skin [ Time Frame: 24 months ]
    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.

  5. α-syn deposits in submandibular gland [ Time Frame: 24 months ]
    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.

  6. α-syn deposits in colon [ Time Frame: 24 months ]
    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.


Biospecimen Retention:   Samples With DNA
Biofluid samplings [blood, saliva, and cerebrospinal fluid (CSF)] Tissue samplings (skin, colon, submandibular gland)


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
Criteria

Inclusion Criteria (PD subjects):

  • 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.

Inclusion Criteria (HC subjects):

  • 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.

Exclusion Criteria (all subjects):

  • 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.

Exclusion criteria (PD subjects):

  • 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.

Exclusion criteria (HC subjects):

  • Has a family history of PD in any first-degree relative.
  • Has a significant neurological disorder (a neurodegenerative condition, clinically significant stroke, brain tumor, hydrocephalus, epilepsy, other neurodegenerative disorders, encephalitis, repeated head trauma, polyneuropathy).
  • Has a Montreal Cognitive Assessment (MoCA) score of less than 26.
  • Has a diagnosis of REM sleep behavior disorder.
  • Has a primary dystonia, restless legs syndrome, essential tremor, or other movement disorder.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02572713


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, Connecticut
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
Canada, Ontario
Toronto Western Hospital Movement Disorders Centre
Toronto, Ontario, Canada, M5T 2S8
Sponsors and Collaborators
Michael J. Fox Foundation for Parkinson's Research
Indiana University
University of Iowa
Banner Health
Paracelsus Elena Klinik
Investigators
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Principal Investigator: Lana Chahine, MD University of Pennsylvania
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Responsible Party: Lana Chahine, MD, Clinical Co-PI, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02572713    
Other Study ID Numbers: S4-001
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: August 2017
Keywords provided by Lana Chahine, MD, University of Pennsylvania:
Parkinson's Disease
alpha-synuclein
biomarker
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases