A Diagnostic Test for Dementia With Lewy Bodies

The Syn-D Study will be evaluating α-synuclein in patients with suspected MCI-AD and MCI-DLB. Using a simple diagnostic test will improve clinical accuracy in diagnosing, earlier diagnosis, and distinguish between neurodegenerative diseases.

Study Overview

• Status: Active, not recruiting
• Conditions: MCI-AD, Early Stage Alzheimer's Disease; MCI-DLB, Early Stage Dementia With Lewy Bodies
• Intervention / Treatment: Diagnostic test: Syn-One Test

Detailed Description

In collaboration with approximately 10 centers that specialize in DLB and dementia we will recruit a total of 80 individuals for the study: 40 subjects with suspected MCI-DLB and 40 with suspected MCI-AD will be recruited. All subjects will be enrolled into a 12 month longitudinal study where skin biopsies will be performed at 3 sites on each patients at 12 month intervals (baseline and 1 year). Detailed quantified examination, cognitive evaluation, history, and questionnaires will be performed at each visit and will be reviewed by a central panel of disease experts to confirm the diagnosis.

Subjects enrolled in the study will have baseline evaluations and follow up visits at 12 months to define any changes to clinical diagnosis. Skin biopsies will be repeated at the 12 month follow up visit to determine the rate of P-SYN accumulation over time and rates of nerve fiber degeneration within punch skin biopsies.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • CND Life Sciences
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
  • Colorado
    • Englewood, Colorado, United States, 80113
      • CenExel RMCR
  • Florida
    • Boca Raton, Florida, United States, 33433
      • University of Miami
    • Winter Park, Florida, United States, 32792
      • Neurology One
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02145
      • Mass General Hospital
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The subjects evaluated in the protocol will have a diagnosis of mild dementia with Lewy bodies (MCI-DLB) or mild Alzheimer's disease (MCI-AD). Patients will be evaluated at Baseline and 12 months. A total of 80 individuals will be enrolled, 40 with MCI-DLB and 40 with MCD-AD, with roughly equal representation of men and women.

All subjects will undergo screening evaluation that includes a thorough medical history, physical and neurologic examination and review of available medical records, laboratory studies, neuroimaging and sleep laboratory studies.

Description

Inclusion Criteria:

1. Men and women 50 to 85 years of age
2. Clinical diagnosis of mild cognitive impairment, and a presumed etiology of DLB or AD at enrollment

Exclusion Criteria:

1. Clinical evidence of severe peripheral vascular disease (Fazekas score of ≥ 3, or a large vessel stroke of ≥ 2 cm, history of ulceration, poor wound healing, vascular claudication)
2. Clinically active coronary artery or cerebrovascular disease
3. Current smoker or alcoholism
4. History of allergic reaction to local anesthesia (for biopsy collection)
5. Use of anticoagulants (aspirin or Plavix alone is allowed)
6. Significantly impaired wound healing or history of scarring or keloid formation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MCI-AD; Will be diagnosed using 'preclinical AD' criteria of mild cognitive impairment supported by a positive biomarker for AD. MCI defined as: 1. History of cognitive decline, noticed by either the patient, family member(s) or a medical practitioner but still independent in most complex daily activities. 2. Documentation of cognition not normal e.g., by MoCA or neuropsychological testing; 3. Does not meet the definition of dementia with MOCA <18 or global CDR 1 or greater (although exceptions may exist with appropriate justification). 4. Supportive AD biomarker (has positive biomarkers for both Aβ and neuronal injury using CSF or neuroimaging).	Diagnostic test: Syn-One Test; CND Life Sciences is expanding the utility of its diagnostic technology, the Syn-One Test, to pathologically distinguish between early DLB and Alzheimer's disease to prevent misdiagnoses and establish the relationship between progression and α-synuclein deposition by measuring α- synuclein accumulation in patient's nerve fibers using a simple skin punch biopsy.
MCI-DLB; Will be diagnosed as prodromal probable MCI-DLB based on consensus criteria using 2 or more core clinical features of DLB (with or without the presence of biomarkers) or 1 or more core clinical features with 1 or more indicative biomarkers (reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET reduced Iodine-MIBG uptake on myocardial scintigraphy, PSG confirmation of REM without atonia).	Diagnostic test: Syn-One Test; CND Life Sciences is expanding the utility of its diagnostic technology, the Syn-One Test, to pathologically distinguish between early DLB and Alzheimer's disease to prevent misdiagnoses and establish the relationship between progression and α-synuclein deposition by measuring α- synuclein accumulation in patient's nerve fibers using a simple skin punch biopsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
This is a prospective longitudinal study of individuals with neurodegenerative DLB and AD disorders to improve the diagnostic precision and utility of the Syn-One TestTM.	To pathologically distinguish DLB from AD early in the course of the disease using the Syn-One TestTM, confirming disease diagnosis through prospective clinical assessments and follow up biopsy analyses over 12 months.	2 years
This is a prospective longitudinal study of individuals with neurodegenerative DLB and AD disorders to improve the diagnostic precision and utility of the Syn-One TestTM.	To define the rates of neuronal degeneration in DLB through systematic pathological quantitation of skin biopsies measuring P-SYN deposition and cutaneous nerve fiber degeneration, compared to AD, and correlating pathological findings with clinical assessments over the course of 12 months.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Aim 1	The outcome measure will be an ordinal quantitation of P-SYN deposition within skin biopsies. The primary endpoint for is sensitivity and specificity of results in DLB and AD. We predict that a threshold of P-SYN >0 is a "positive" result and will separate DLB from AD using dichotomous measures, but ROC curve analysis will be performed to maximize sensitivity and specificity using continuous quantitative measurement of P- SYN.	2 years
Secondary Aim 2	Will include P-SYN deposition, SGNFD, PMNFD and IENFD as continuous variables for statistical analysis. Data will be compared first using repeated measures Analysis of Covariance (ANCOVA), with DLB as the predictor variable. The primary dependent variable is the quantitative measure of P-SYN deposition.	2 years

Collaborators and Investigators

• Sponsor: CND Life Sciences
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Todd Levine, MD, CND Life Sciences

Publications and helpful links

General Publications

• Gibbons CH, Freeman R, Bellaire B, Adler CH, Moore D, Levine T. Synuclein-One study: skin biopsy detection of phosphorylated alpha-synuclein for diagnosis of synucleinopathies. Biomark Med. 2022 May;16(7):499-509. doi: 10.2217/bmm-2021-0646. Epub 2022 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Estimated): September 28, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Alzheimer Disease; Dementia; Lewy Body Disease
• Other Study ID Numbers: 101 (Other Identifier: Hamilton Integrated Research Ethics Board); R44AG076072 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be shared with researchers that are involved in the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No