Objective: This study will explore how the brain areas important for attention and short-term memory might be contributing to some of the movement issues seen in persons with Parkinson’s Disease. Sessions will involve magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS).

Inclusion criteria:

• Parkinson disease (PD) with PD diagnosis based on the recent Movement Disorder Society criteria.
• PD subjects >45 years and <91 will be studied.
• H&Y1-2 (early PD) subjects will be recruited.
• Only PD subjects on stable dopamine replacement therapy will be recruited.

Exclusion criteria:

• The presence of other neurologic disease or neurologic findings on examination.
• Depression: Geriatric Depression Scale (GDS) score >11.
• Evidence of a stroke or mass lesion on prior structural brain imaging (CT or MRI).
• Evidence of any confounding medical or psychiatric problem that would preclude task participation.
• Metallic medical implants (i.e. pacemaker), foreign objects in body, non-removable body-piercings
• Pregnancy

Additional exclusion criteria related to TMS:

• Metal in the cranium (mouth excluded)
• Cardiac pacemaker
• Implanted medication pump
• Implanted deep brain stimulator or vagus nerve stimulator
• Intracardiac lines
• Serious heart disease
• Increased intracranial pressure
• History of seizures
• Epileptogenic medication
• Cochlear implants
• Recent extended air travel resulting in jetlag or other sleep deprived state

Coordinator: Queen Bolden [email protected];  Teresa Scerbak [email protected]

Objective: Advance our understanding of progressive cholinergic changes within specific subcortical and cortical structures subserving cognitive and attentional-motor integration functions in PwP at risk of dementia, balance and gait disturbances.

Inclusion Criteria:

• Age 45 and above (M/F).
• PD diagnosis (with or without Mild Cognitive Impairment) will follow the Movement Disorder Society-revised clinical diagnostic criteria for PD (7). Absence of dementia confirmed by neuropsychological testing. Modified Hoehn and Yahr stages 1-4 (8, 9).
• All PD subjects are required to have nigrostriatal dopaminergic denervation as demonstrated by vesicular monoaminergic transporter type-2 (VMAT) [¹¹C]DTBZ positron emission tomography (PET) imaging. This may be based on a prior DTBZ PET scan or the DTBZ PET scan performed as part of this study.

Exclusion Criteria:

• Presence of clinically significant dementia.
• Disorders which may resemble PD, such as dementia with Lewy bodies, vascu­lar dementia, normal pressure hydrocephalus, multiple system atrophy, corticobasal ganglionic dege­neration, or toxic causes of parkinsonism. The use of the Movement Disorder Society-revised clinical diagnostic criteria will mitigate the inclusion of PD subjects with atypical parkinsonism.
• Subjects on neuroleptic, anticholinergic (trihexiphenidyl, benztropine), or cholinesterase inhibitor drugs. Subjects with prior exposure to disallowed medications may be eligible if there has been an interval of > 2 months off these medications.
• Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI or CT).
• Participants in whom MRI is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
• Severe claustrophobia precluding MR or PET imaging.
• Subjects limited by previous participation in research procedures involving ionizing radiation.
• Pregnancy (test within 48 hours of each PET session) or breastfeeding.
• History of deep brain stimulation surgery.
• Suicidality (responses 2 or 3 for question 9 on the Beck Depression Inventory).

Coordinator: Austin Luker [email protected]

Objective: to continue to obtain information from people with and without Parkinson disease so that researchers may better understand how PD progresses, in order to inform better treatments.  Study procedures include DaTscan, MRI, Lumbar puncture and skin biopsy.

Inclusion Criteria:

• 30+ years old
• PD diagnosed w/in 2 years
• Not expected to require PD medication within at least 6 months from Baseline
• Must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting tremor or bradykinesia); OR either asymmetric resting tremor or asymmetric bradykinesia
• Hoehn and Yahr stage I or II
• Confirmation that participant is eligible based on Screening DaTscan imaging
• Treatment naive

Exclusion:

• Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or another PD medication.
• Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days of Baseline visit.
• Received any of the following drugs: dopamine receptor blockers, metoclopramide and reserpine within 6 months of Screening visit.
• A clinical diagnosis of dementia
• Previously obtained MRI scan with evidence of clinically significant neurological disorder
• Current treatment with anticoagulants that might preclude safe completion of the lumbar puncture.

Coordinator: Frank Ferrari [email protected]; Kim Duval [email protected]; Angela Stovall [email protected]

Objective: To explore how levodopa treatment in PD produces the Long Duration Response (LDR).

Inclusion Criteria:

• PD diagnosis
• Previously untreated
• H&Y I or II
• Age >45 and <81

Exclusion Criteria:

• Presence of other neurologic disease or findings on examination
• Cognitive impairment: MoCA score of <24
• Depression: GDS score of >5
• Use of dopamine agonists or stimulants
• Evidence of a stroke or mass lesion on prior structural brain imaging (MRI or CT)
• Evidence of any confounding medical or psychiatric problem that would preclude task participation

Procedures:

• Demographic Data
• Clinical Rating Scales: UPDRS, PD-CRS, GDS, Lille Apathy Scale, etc.
• Simple Tests of Motor Function, Motivational Function

Coordinator: Teresa Scerbak [email protected] 

Objective: To evaluate diagnostic performance of free water MR imaging to help with the differential diagnosis of atypical parkinsonism.

Inclusion Criteria:

• Possible/probable MSA-P
• Possible probable PSP

Exclusion:

• Contra-indication to MRI
• Claustrophobia
• Pregnant or nursing women

Coordinator: Jaimie Barr [email protected]

Objective: to learn more about the effects of aerobic exercise on people with Parkinson’s disease who have not yet started medication for their PD. It will compare the effects of moderate intensity (60-65% HRmax) treadmill exercise to high intensity (80-85% HRmax) treadmill exercise on the signs and symptoms of Parkinson’s disease.

Inclusion criteria:

• Primary Parkinson’s Disease diagnosed using UK Brain Bank Criteria (< 3 years since diagnosis)
• Age 40-80 years
• Hoehn and Yahr stage less than 3

Exclusion criteria:

• Currently treated with dopaminergic therapies or expected to require such treatment within next 6 months
• Use of PD medication within past 60 days
• Poorly controlled or unstable cardiovascular, metabolic, or renal disease
• Hypertension, hypo- or hyperthyroidism, and/or abnormal renal function. Orthostatic hypotension & standing systolic BP < 100
• Disorders that interfere with ability to perform endurance exercises
• >120 minutes/week moderate intensity endurance exercise for more than 6 months
• MoCA score <26, BDI score >16
• Prior SPECT scan within past 6 months
• Allergy to iodinated products/hypersensitivity to DaTscan™ SPECT
• Women who are pregnant or plan to become pregnant in next 12 months

Coordinator: Jake Fogel [email protected]

Inclusion:

• Men and women with a diagnosis of PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Research Criteria

• Age 45 and older

• Hoehn & Yahr Stages 1-2.5

Exclusion:

• Any recent changes in EKG, history of myocardial infarction or other cardiac event or other cardiac contraindications to exercise

• Inability to use a step, stand, walk, or use a stationary cycle ergometer;  

• History of symptoms in exercise that preclude safe and comfortable participation, such as dizziness and lightheadedness, orthostasis, severe symptomatic leg or back musculoskeletal pain, painful neuropathy, significant ankle edema or medication side effects;  

• History of symptomatic cardiovascular or pulmonary disease interfering with exercise;  

• History of active rheumatoid arthritis;  

• History of uncontrolled chronic pain syndrome;  

• Any other history of medical or psychiatric comorbidity precluding safe participation in the project;  

• Poorly controlled diabetes

• Pregnancy or breastfeeding

• Clinically significant dementia

Coordinator: Austin Luker [email protected]

Objective: This study will examine the potential of CVN424 (a GPR6 inverse agonist) to improve motor and non-motor functions in individuals with early untreated Parkinson’s Disease (PD). Participants will be randomized to receive CVN424 150 mg or placebo over 12 weeks and attend visits every 2 weeks.

Inclusion Criteria:

1. Diagnosis of PD

2. Untreated for PD and not expected to require treatment for duration of study (18 weeks)

3. Age ≥ 30

4. Modified Hoehn and Yahr ≤ 2.5

5. Montreal Cognitive Assessment (MoCA) ≥ 26

Exclusion Criteria:

1. Diagnosis of secondary or atypical parkinsonism

2. Diagnosis of parkinsonian motor signs or symptoms ≥ 4 years ago

3. Previous surgical procedure for PD

4. Prior treatment with a dopamine agonist, levodopa, MAOB inhibitor, or adenosine A2A receptor antagonists for ≥ 28 days

5. Current use of any antipsychotic, metoclopramide, or reserpine

6. Current use of potent Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers

7. Clinically significant orthostatic hypotension

8. Clinically significant hallucinations requiring antipsychotic use

9. Potentially unstable heart disease

10. Current (or within past 12 months) diagnosis or history of substance abuse disorder

11. Marijuana use within 2 months of the Screening Visit

12. Currently active major depression

13. Active suicidal ideation within 1 year prior to Screening Visit

14. Positive test for HIV, HBV, HCV consistent with current infection

Coordinator: Teresa Scerbak ([email protected]) and Angela Stovall ([email protected])

This is a randomized, double-blinded, placebo control trial to assess Celeste Specialized Phototherapy in treatment of PD symptoms. This device emits a specific frequency of blue and green light, with the primary outcome measure being improvement in the PDQ-39. Participants will need to use the light device for 1 hour in the evening for the duration of the study.  This is a 6 mo. trial with ONLY virtual visits for screening, baseline, 3 mo. and 6 mo. Participants are randomized 1:1 to the Celest device or an identical device emitting a non-therapeutic level of light.

Inclusion:

45yo+ with iPD on treatment with good response for at least 1 year.

Stable levodopa dosing for 30 days prior to screening

Exclusion:

Significant eye disease (visual acuity less than 20/60 with correction)

Significant OFF time of dyskinesia that would interfere with ability to participate in therapy

MoCA < 24

Prior light therapy study participation

Current MDD requiring medication changes

Working swing shifts

For interested participants, please send their information through email or provide the following link: https://celestepd.squarespace.com/

You can also use the following dot phrase (LIGHTPD) in their check-out paperwork. This marketing information is IRB approved.

ATLANTIS: A Phase 2 study assessing for safety, tolerability, pharmacokinetics, and efficacy of a selective positive allosteric modulator of the D1 receptor for the treatment of motor fluctuations. (PI: Wyant)

Inclusion Criteria:

• 45 years or older with PD for 5 or more years

• Has fluctuations with at least 2.5 hours of off-time per day

Exclusion Criteria:

• Taking rescue medications (Inbrija, Apokyn)

• Pharmacologic treatment for OH

• Dementia or MoCA < 23

• Taking antipsychotics including quetiapine

• Significant hypertension, liver or kidney dysfunction, cancer (other than skin cancer) in 5 years

• EKG with normal QTc

Coordinators: Cate Cochren ([email protected]) and Angela Stovall ([email protected])

A Phase I/II, Randomized, Double-blind, Sham Control Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington Disease

Objective: demonstrate safety and tolerability of AMT-130 when delivered directly to the brain by evaluating changes in safety parameters out to 5 years post AMT-130 treatment in genetically confirmed, early manifest HD patients.

Inclusion Criteria:

• 25-65 years of age
• Clinical diagnosis of early manifest HD
• Total Functional Capacity Score (TFC) 9-13
• Diagnosis Confidence Level (DCL) 4 or
• DCL of 3 with either a positive (“Yes”) response to the UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder
• CAG repeat ≥ 40
• HD con meds stable for 3 months prior to screening
• Putamen volume of ≥2.5 cm3 (per side) and a caudate volume of ≥2.0 cm3 (per side) on MRI

Exclusion Criteria:

• Suicidal risk
• Contraindication to MRI or LP
• Malignancy in past 5 years
• History of gene therapy
• Significant neurologic comorbid disorder or brain and spinal pathology that may interfere with the surgical delivery of AMT-130

Coordinator: Angela Stovall [email protected]

Objective: Worldwide longitudinal observational study of Huntington’s disease (HD) whose overarching goal is to accelerate progress towards the development of effective therapeutics for HD

Inclusion Criteria:

• Carriers:
  • Individuals who carry the HD gene expansion mutation (stage 1 and 2 only)
• Controls:
  • Individuals who do not carry the HD expansion mutation
    • First or second degree relatives to a carrier;
    • Family members or individuals not related by blood to carriers (e.g. spouses, caregivers); or
    • Community controls, which are individuals unrelated to HD carriers who did not grow up in a family affected by HD

Exclusion Criteria:

• Individuals with choreic movement disorders in the context of a negative test for the HD gene mutation
• For community controls: individuals with a major central nervous system disorder (e.g. stroke, Parkinson’s disease, Multiple Sclerosis, etc.)

Coordinator: Aadi Nalla [email protected]; Chris Graves [email protected]