N-Acetyl Cysteine + FDOPA PET for Parkinson's Disease

(FdopaPD2 Trial)

Overseen By Nancy A Wintering, MSW

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Must be taking: Antiparkinsonian medications

Must not be taking: Blood pressure, Blood clotting, Diabetes, Nitroglycerin

Disqualifiers: Cognitive impairment, Psychiatric disorder, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months ± 3 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if NAC, a cell-protecting supplement, can help people with Parkinson's disease by improving their dopamine function. NAC boosts a protective substance in the brain, potentially keeping dopamine-producing cells healthy. NAC has been studied for its potential to support dopamine neurons and improve motor function in Parkinson's disease due to its antioxidant properties.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you need to be on stable Parkinson's medication for at least one month before joining. If you're taking medications that might interact with NAC, the study doctor will evaluate your situation individually.

Is N-Acetyl Cysteine safe for humans?

N-Acetyl Cysteine (NAC) has been used in studies with Parkinson's disease patients and healthy individuals, showing some antioxidant benefits. However, some participants reported mild side effects, and more research is needed to fully understand its safety profile. ^{1 2 3 4 5}

How does the drug N-acetyl cysteine differ from other treatments for Parkinson's disease?

N-acetyl cysteine (NAC) is unique because it acts as an antioxidant that may protect and support dopamine neurons, potentially improving dopamine function in the brain. Unlike standard treatments, NAC is administered both intravenously and orally, and it may offer neuroprotective benefits by increasing dopamine transporter binding, which is not a typical feature of other Parkinson's treatments. ^{2 3 4 6 7}

What evidence supports the effectiveness of the treatment N-Acetyl Cysteine + FDOPA PET for Parkinson's Disease?

Research shows that FDOPA PET imaging can help visualize and measure the damage in the brain's dopamine system in Parkinson's disease, which is important for understanding disease progression. This imaging technique has been used to track how the disease progresses and to evaluate potential treatments. ^{8 9 10 11 12}

Who Is on the Research Team?

Daniel A Monti, MD, MBA

Principal Investigator

TJU, Dept. Chair: Integrative Medicine and Nutritional Sciences

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease patients aged 30+, on stable medication, with a Hoehn and Yahr score of I-III. They must be physically independent and not pregnant or planning surgery. Exclusions include allergies to NAC, previous brain surgeries, severe cognitive impairment, non-ambulatory status, significant psychiatric disorders, substance abuse issues, recent participation in other trials or therapies.

Inclusion Criteria

I am 30 years old or older.

My Parkinson's disease is in the early to mid-stage.

I am using effective birth control as my partner can have children.

Exclusion Criteria

I have controlled diabetes, GERD, or thyroid conditions.

I have had brain surgery before.

Pregnant or lactating women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral and intravenous N-acetyl Cysteine (NAC) in addition to standard of care for Parkinson's Disease

6 months ± 3 months

Weekly visits for IV administration, daily oral administration

Crossover

Participants switch arms; those initially receiving NAC switch to standard care and vice versa

6 months ± 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months ± 3 months

What Are the Treatments Tested in This Trial?

Interventions

• [F-18] Fluorodopa Positron Emission Tomography
• N acetyl cysteine

Trial Overview The study tests how N Acetyl Cysteine (NAC) supports dopamine function in Parkinson's patients using PET-MRI scans before and after treatment. Participants will receive oral capsules plus IV infusions of NAC alongside standard care over approximately six months in an open-label crossover design.

How Is the Trial Designed?

Group I: Waitlist Control Cohort Experimental Treatment 1 Intervention

Standard of Care Treatment for approximately 6 ±3 months.

Group II: Oral and IV N acetyl Cysteine Cohort Experimental Treatment 2 Interventions

Administration of Intravenous (IV) and Oral N-acetyl Cysteine (NAC) Intervention: IV NAC infusion: Dose: 50mg in 200ml of Dextrose 5% in Water (D5W), frequency: over one hour 1 x per week for 90 days ± 30 days AND Oral N-acetyl Cysteine - one 500 mg tablet 2 x per day (on days IV N-acetyl cysteine is not administered). Oral NAC will be taken for approximately 6 ±3 months.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Published Research Related to This Trial

Using high-resolution PET/CT scans with 18F-FDOPA and 11C-raclopride, this study found that both tracers showed higher uptake in normal subjects compared to previous studies, indicating improved imaging capabilities.

The study demonstrated that 18F-FDOPA uptake in the substantia nigra can be clearly visualized, providing valuable insights for evaluating regenerative therapies in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A revisit to quantitative PET with 18F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy. Akamatsu, G., Ohnishi, A., Aita, K., et al.[2017]

Current molecular PET imaging techniques for neurodegenerative parkinsonism focus on radiotracers that visualize vulnerable neuron terminals, but they do not effectively differentiate between various parkinsonian conditions based on neurotransmitter loss.

Research is ongoing to develop new imaging ligands using advanced molecular modeling to better target specific proteinopathies associated with these disorders, although current PET imaging methods face challenges such as the need for automated analysis and limited insurance coverage in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging of Neurodegenerative Parkinsonism. Frey, KA., Bohnen, NILJ.[2021]

F-18 FDOPA PET imaging shows high specificity (91%) and positive predictive value (92%) for detecting dopaminergic degeneration in patients with Parkinson's disease, indicating it is a reliable tool for diagnosis.

The study, involving 68 parkinsonian subjects, found moderate sensitivity (73%) for the imaging technique, and it received FDA approval in October 2019, highlighting its potential as a diagnostic method in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective F-18 FDOPA PET Imaging Study in Human PD. Dhawan, V., Niethammer, MH., Lesser, ML., et al.[2023]

6-[18F]-fluorodopa (FDOPA) is an effective PET imaging agent that helps visualize presynaptic dopaminergic function in the brain, making it valuable for diagnosing Parkinson's disease and differentiating it from other forms of parkinsonism.

FDOPA can also be used to study the pharmacokinetics of L-DOPA and evaluate its effects on dopamine metabolism, enhancing our understanding of treatment responses in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[PET study using 6-[18F]-fluorodopa in Parkinson's disease]. Nagasawa, H., Tanji, H., Itoh, M., et al.[2016]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

SPECT and PET imaging of the dopaminergic system in Parkinson's disease. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Rate of 6-[18F]fluorodopa uptake decline in striatal subregions in Parkinson's disease. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

A revisit to quantitative PET with 18F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Molecular Imaging of Neurodegenerative Parkinsonism. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Prospective F-18 FDOPA PET Imaging Study in Human PD. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

N-acetylcysteine decreases dopamine transporter availability in the non-lesioned striatum of the 6-OHDA hemiparkinsonian rat. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Systemic administration of N-acetylcysteine protects dopaminergic neurons against 6-hydroxydopamine-induced degeneration. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

[PET study using 6-[18F]-fluorodopa in Parkinson's disease]. [2016]