Parkinson Disease
Conditions
Brief summary
This study will evaluate the feasibility of adding objective measures (FDG-PET imaging, wearable biosensors) to a week-long washout protocol in early-stage Parkinson's disease patients. This study is also determining whether the washout can be conducted in the ambulatory setting.
Interventions
None listed
Sponsors
Vanderbilt University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. \*A clinical diagnosis of idiopathic PD. The diagnosis will be based upon the presence of at least two of the three cardinal motor signs of this disorder (akinesia/bradykinesia, rest tremor, and rigidity) with at least one of the signs being rest tremor or bradykinesia. 2. Clear and dramatic beneficial response to dopaminergic therapy (defined as demonstrating at least 30% improvement in parkinsonian motor signs based upon the UPDRS-III motor examination subscore, following the administration of their dopaminergic medications during the screening neurological examination) 3. \*Hoehn and Yahr (H\&Y) stage II when off medication. 4. Age between 50 and 75 years. 5. Subjects must be on dopaminergic therapy for at least one year prior to the screening visit and less than four years prior to the completion of the washout period. 6. Subjects must have a stable response to dopaminergic medication. 7. Available for follow-up for the entire duration of the study. 8. Subjects receiving antidepressant medication used specifically for the treatment of depression must be on stable doses for at least eight weeks prior to enrolling in the study. 9. Subjects must agree to maintain a stable regimen, if deemed medically appropriate by the treating physician, of any psychotropic medications throughout the study.
Exclusion criteria
1. \*Evidence of an alternative diagnosis or secondary parkinsonism, as suggested by: 1. Features unusual early in the clinical course (e.g., prominent postural instability, freezing phenomena, or hallucinations unrelated to medications in the first 3 years after symptom onset) 2. Dementia preceding motor symptoms 3. Neurologic signs of upper motor neuron or cerebellar involvement 4. Significant orthostatic hypotension unrelated to medications 5. Unequivocal cortical sensory loss (i.e., graphesthesia, stereognosis with intact primary sensory modalities), clear limb ideomotor apraxia, or progressive aphasia 6. Vertical supranuclear gaze palsy, or selective slowing of vertical saccades 7. Unequivocal cerebellar abnormalities on examination, such as cerebellar gait, limb ataxia, or cerebellar oculomotor abnormalities (e.g., sustained gaze-evoked nystagmus, macro square wave jerks, hypermetric saccades) 8. Documentation of a condition known to produce parkinsonism and plausibly connected to the subject's symptoms (e.g., history of stroke, exposure to toxins, or encephalitis; or neuroleptic use within the past 6 months) 2. \*The expert evaluating physician, based on the full diagnostic assessment, believes that an alternative syndrome is more likely than PD. 3. \*Uncontrolled medical condition or clinically significant medical disease that would increase the risk of developing pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension). 4. \*Evidence of existing dyskinesias. 5. \*Diagnosis of probable behavioral variant frontotemporal dementia or primary progressive aphasia. 6. \*Currently active diagnosis of a major psychiatric disorder 7. Previous brain operation or injury. 8. Active participation in another clinical trial for the treatment of PD. 9. \*Any current substance use disorder. 10. Any history of recurrent or unprovoked seizures. 11. Any prior movement disorder treatments that involved intracranial surgery or device implantation. 12. Any active implanted intracranial device (e.g., cochlear implant) or implanted device to treat movement disorders (e.g., duodopa pump) whether turned on or off. 13. History of suicide attempt. 14. A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception. 15. Inability or unwillingness of subject to give written informed consent. 16. \*Parkinsonian features restricted to the lower limbs for more than three years. 17. \*Treatment with a dopamine receptor blocker or a dopamine-depleting agent in a dose and timecourse consistent with drug-induced parkinsonism. 18. Rapid progression of gait impairment requiring regular use of a wheelchair. 19. \*Early bulbar dysfunction, defined as one of severe dysphonia, dysarthria (speech unintelligible most of the time), or dysphagia \[requiring soft food, nasogastric (NG) tube, or gastrostomy feeding\]. 20. \*Inspiratory respiratory dysfunction defined as either diurnal or nocturnal inspiratory stridor or frequent inspiratory sighs. 21. \*Recurrent (\>1/year) falls because of impaired balance within 3 years of onset. 22. \*Otherwise unexplained pyramidal tract signs, defined as pyramidal weakness or clear pathologic hyperreflexia (excluding mild reflex asymmetry in the more affected limb and isolated extensor plantar response). 23. \*Bilateral symmetric parkinsonism throughout the disease course. The patient or caregiver reports bilateral symptom onset with no side predominance, and no side predominance is observed on objective examination. 24. Received radiation exposure as part of other recent research studies and individuals who work around radiation will be excluded from the study 25. Subjects who do not pass the neuropsychological screening battery. 26. \*Subjects who, in the opinion of the study neurologist or principal investigator, should not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Parkinson's Disease Related Pattern (PDRP) Z-Score From ON Medications to One-week OFF Medications | Day 1 and Day 8 | The Parkinson's Disease-Related Pattern (PDRP) is a disease-specific metabolic brain network derived from fluorodeoxyglucose positron emission tomography (FDG-PET) that reflects Parkinson's disease-related abnormalities in regional cerebral glucose metabolism. Individual PDRP scores represent standardized network expression values (z-scores; A Z-score of 0 represents the population mean) calculated relative to a reference population; there is no fixed minimum or maximum score. Higher values indicate greater expression of the Parkinson's disease metabolic pattern. Change was calculated as Day 8 OFF medication score minus Day 1 ON medication score. |
| Changes in the Parkinson's Disease Cognitive Pattern (PDCP) Z-Score From ON Medications to One-week OFF Medications | Day 1 and Day 8 | The Parkinson's Disease Cognitive Pattern (PDCP) is a disease-related metabolic brain network derived from fluorodeoxyglucose positron emission tomography (FDG-PET) that reflects metabolic abnormalities associated with cognitive dysfunction in Parkinson's disease. PDCP scores represent standardized network expression values (z-scores; Z-score of 0 represents the population mean) calculated relative to a reference population; there is no fixed minimum or maximum score. Higher values indicate greater expression of the Parkinson's disease cognitive metabolic pattern. Change was calculated as Day 8 OFF medication score minus Day 1 ON medication score. |
| Daily Kinesia ONE Finger Tapping Speed Scores Over a One-week Medication Washout | Day 1 through Day 8 | Finger tapping speed was measured using the Kinesia ONE wearable motion sensor system during standardized finger tapping tasks. Accelerometer data were used to generate quantitative finger tapping speed scores reflecting bradykinesia severity. Left and right finger tapping scores were calculated separately and averaged to generate a single daily value for each participant. Scores range from 0 to 4, with higher values indicating greater bradykinesia severity (worse motor impairment). Measurements were recorded daily during the one-week dopaminergic medication washout. |
| Daily Kinesia ONE Rest Tremor Scores Over a One-week Medication Washout | 1 week | Rest tremor severity was measured using the Kinesia ONE wearable motion sensor system during standardized tremor assessments. Accelerometer data were used to generate quantitative tremor severity scores. Left and right tremor scores were calculated separately and averaged to generate a single daily value for each participant. Scores range from 0 to 4, with higher values indicating greater tremor severity (worse motor impairment). Measurements were recorded daily during the one-week dopaminergic medication washout. |
| Number of Participants With Adverse Events Related to the Medication Washout | 1 week | Number of participants experiencing an adverse event judged by the study neurologist to be related to the dopaminergic medication washout during the study period. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 65.7 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Levodopa Equivalent Daily Dose (LEDD) | 490 mg/day STANDARD_DEVIATION 414 |
| PD medication (years) | 1.7 years STANDARD_DEVIATION 0.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
| Unified Parkinson's Disease Rating Scale, Part III improvement ON medication (%) at screening | 59 percentage change STANDARD_DEVIATION 15 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Part-III overnight OFF medication at screening | 28.3 units on a scale STANDARD_DEVIATION 6.5 |
| UPDRS-III ON medication at screening | 12.3 units on a scale STANDARD_DEVIATION 6.3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
None listed