Trial Outcomes & Findings for Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy. (NCT NCT01380899)
NCT ID: NCT01380899
Last Updated: 2021-05-25
Results Overview
The presence in the brain of a-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of alpha-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. First, our goal was to demonstrate the presence of alpha-synuclein inclusions in the skin of PD patients. Second, to detect quantitative differences (measures in the percentage of presence in the skin´s cells) between patients with PD, atypical parkinsonism (AP), compared with an apparent healthy group.
COMPLETED
87 participants
An average of seven days.
2021-05-25
Participant Flow
Skin retro auricular biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for a-synuclein, after which its presence was quantified as the percentage of positive cells (containing alpha-synuclein). Patients were divided into those with Parkinson's Disease (PD: 34) and those with Atypical Parkinsonism (AP: 33). AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP
PD used the United Kingdom PD Society Brain Bank. Lewy body dementia (LBD) used the consortium report on the DLB international workshop. AD used the recommendations from the National Institute on Aging and Alzheimer's Association workgroups on diagnostic guidelines for AD. MSA used the Second consensus statement on the diagnosis of multiple system atrophy. PSP used the report of the NINDS-SPSP International Workshop.
Participant milestones
| Measure |
Parkinson Disease
Patients with Parkinson Disease (PD) PD is the patient initially presented asymmetric onset (with both rest and postural tremors with a frequency of between 5 and 7 Hz), rigidity, bradykinesia, postural instability, an acceptable and sustained response to levodopa, and previous and concomitant nonmotor characteristic semiology.
|
Atypical Parkinsonism
AP was divided into primary (neurodegenerative) and secondary (postencephalitic, vascular, drug-induced, toxic) groups.
The neurodegenerative included patients with the diagnosis of Lewy body dementia (LBD) used the consortium report on the DLB international workshop.
Patients with the diagnosis of AD used the recommendations from the National Institute on Aging and Alzheimer's Association workgroups on diagnostic guidelines for AD.
Patients with the diagnosis of MSA used the Second consensus statement on the diagnosis of multiple system atrophy.
The diagnosis PSP used the report of the NINDS-SPSP International Workshop. CBS and we included a case with a diagnosis of neurodegeneration with brain iron accumulation syndrome (NBIA).
Most of these criteria are summarized in the SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders.
|
Control Group
Subjects apparently in a good state of health without antecedents of neurodegenerative diseases and not symptoms or signs of neurodegeneration (comparable with the group's problem in gender, age, and population characteristics).
|
|---|---|---|---|
|
Overall Study
STARTED
|
34
|
33
|
20
|
|
Overall Study
COMPLETED
|
34
|
33
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.
Baseline characteristics by cohort
| Measure |
Parkinson Disease
n=34 Participants
Patients with Parkinson Disease: 34 Average. Age (mean SD) 66.82 (+11.4)
|
Atypical Parkinsonism
n=33 Participants
Participants with Atypical Parkinsonism degenerative (26) or secondary (7), total: 33
|
Control Group
n=20 Participants
Subjects without neurodegenerative disease and apparently good state of health (20)
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
64 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
23 Participants
n=483 Participants
|
|
Age, Continuous
|
66.82 years
STANDARD_DEVIATION 11.4 • n=93 Participants
|
68.2 years
STANDARD_DEVIATION 13.5 • n=4 Participants
|
74 years
STANDARD_DEVIATION 7.9 • n=27 Participants
|
69.6 years
STANDARD_DEVIATION 10.9 • n=483 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
32 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
55 Participants
n=483 Participants
|
|
Region of Enrollment
Mexico
|
34 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
87 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: An average of seven days.Population: PD diagnosis is made if bradykinesia is associated with rigidity, tremor, or postural instability and unilateral onset and persistent asymmetry, excellent response to levodopa, severe levodopa-induced dyskinesia, and progression. AP are other neurodegenerative diseases with parkinsonism or related to strokes, head injuries, encephalitis, neuroleptic use, toxins, cerebral tumor, hydrocephalus. The Control group was a comparable population without parkinsonism and apparently healthy.
The presence in the brain of a-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of alpha-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. First, our goal was to demonstrate the presence of alpha-synuclein inclusions in the skin of PD patients. Second, to detect quantitative differences (measures in the percentage of presence in the skin´s cells) between patients with PD, atypical parkinsonism (AP), compared with an apparent healthy group.
Outcome measures
| Measure |
Parkinson Disease
n=34 Participants
Patients with the clinical diagnosis of Parkinson Disease
|
Atypical Parkinsonism
n=33 Participants
Atypical parkinsonian conditions mainly comprise progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multisystem atrophy (MSA), and dementia with Lewy bodies (DLB). Apart from these sporadic neurodegenerative disorders, atypical parkinsonism has also been described in various other inherited degenerative conditions such as frontotemporal dementia (FTD), Alzheimer's disease, and Perry syndrome. Nondegenerative parkinsonisms include vascular, toxic (use of neuroleptics, exposure to manganese, carbon monoxide, etc.), and traumatic.
|
Control Group
n=20 Participants
Apparently, healthy subjects without a family history of neurodegenerative or chronic diseases could have population characteristics comparable to the problem groups' participants.
|
|---|---|---|---|
|
Demonstrate the Presence of Alpha-Synuclein Inclusions in the Skin of Parkinson's Disease and Compare With an Atypical Parkinsonism Group and With a Healthy Control Group.
Pilosebaceus unit
|
62.1 percentage of expression
Interval 48.5 to 71.2
|
7.7 percentage of expression
Interval 0.0 to 20.7
|
0 percentage of expression
Interval 0.0 to 0.0
|
|
Demonstrate the Presence of Alpha-Synuclein Inclusions in the Skin of Parkinson's Disease and Compare With an Atypical Parkinsonism Group and With a Healthy Control Group.
Epidermis. Alpha synuclein expresion
|
57.9 percentage of expression
Interval 44.9 to 62.6
|
6.9 percentage of expression
Interval 0.0 to 18.3
|
0 percentage of expression
Interval 0.0 to 1.7
|
|
Demonstrate the Presence of Alpha-Synuclein Inclusions in the Skin of Parkinson's Disease and Compare With an Atypical Parkinsonism Group and With a Healthy Control Group.
Eccrine gland
|
58.4 percentage of expression
Interval 47.4 to 69.3
|
0 percentage of expression
Interval 0.0 to 0.0
|
0 percentage of expression
Interval 0.0 to 0.0
|
Adverse Events
PD (n = 34)
Atypical Parkinsonism (n=33)
Control Group (n=20)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PD (n = 34)
n=34 participants at risk
We enrolled 34 participants who had PD.
|
Atypical Parkinsonism (n=33)
n=33 participants at risk
A total of 33 patients had AP: from they 26 were found to have a neurodegenerative disease clinically (18 had a synucleinopathy-related diagnosis: MSA, LBD, and 8 had tauopathies: PSP, AD). We also included seven patients with secondary parkinsonism.
|
Control Group (n=20)
n=20 participants at risk
A control group (n = 20) of similar age and sex distribution to the patient population was included. There was no significant difference in either age or evolution of disease between the two groups with parkinsonism.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Transient bleeding
|
2.9%
1/34 • The participants were aware of the possibles adverse events that they could present (pain and bleeding in the site where the biopsy was talked) during the seven days following the biopsy.
Three possible EA were systematically advertised to the patients: 1. Pain in the retro-auricular area where the biopsy was taken. 2. Bleeding in the site of the biopsy. 3. A potential danger of infection in the place of the biopsy. All of them are graduated as AE grade 1, according to the CTCAE. No one event serious event was reported.
|
3.0%
1/33 • The participants were aware of the possibles adverse events that they could present (pain and bleeding in the site where the biopsy was talked) during the seven days following the biopsy.
Three possible EA were systematically advertised to the patients: 1. Pain in the retro-auricular area where the biopsy was taken. 2. Bleeding in the site of the biopsy. 3. A potential danger of infection in the place of the biopsy. All of them are graduated as AE grade 1, according to the CTCAE. No one event serious event was reported.
|
0.00%
0/20 • The participants were aware of the possibles adverse events that they could present (pain and bleeding in the site where the biopsy was talked) during the seven days following the biopsy.
Three possible EA were systematically advertised to the patients: 1. Pain in the retro-auricular area where the biopsy was taken. 2. Bleeding in the site of the biopsy. 3. A potential danger of infection in the place of the biopsy. All of them are graduated as AE grade 1, according to the CTCAE. No one event serious event was reported.
|
Additional Information
Ildefonso Rodriguez-Leyva
Facultad de Medicina, Universidad Autonoma de San Luis Potosi
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place