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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how N-Acetyl Cysteine (NAC) might support dopamine levels in the brains of people with Parkinson's disease. Participants will receive NAC through capsules and infusions, alongside their usual Parkinson's care. Researchers will use advanced brain imaging ([F-18] Fluorodopa Positron Emission Tomography) to study changes. Ideal candidates for this trial are those with Parkinson's who can walk independently and have been on stable medication for at least a month. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetyl cysteine (NAC) is generally safe for use. Smaller human studies demonstrated that NAC can reach the brain and was well-tolerated. Some participants even showed slight improvements in movement and brain scans. Recent trials used NAC doses ranging from 1200 to 8000 mg per day for 4 weeks to 6 months, and these studies found no major safety concerns. Although NAC is considered safe, excessive intake can be risky. Following dosing instructions carefully is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Researchers are excited about N-acetyl cysteine (NAC) for Parkinson's Disease because it offers a potential new way to support brain health. Unlike standard treatments that primarily focus on managing symptoms with dopamine replacement, NAC is believed to work by replenishing antioxidants and reducing oxidative stress in the brain, which might slow disease progression. Additionally, NAC is administered both orally and intravenously, providing flexibility in how treatment is delivered. This dual delivery method could enhance the overall effectiveness of NAC, making it a promising addition to existing Parkinson's therapies.

What evidence suggests that N-acetyl cysteine might be an effective treatment for Parkinson's disease?

Research has shown that N-acetyl cysteine (NAC), which participants in this trial may receive, might benefit people with Parkinson's disease. In previous studies, patients experienced about a 13% improvement in their symptoms, measured using a common tool for assessing Parkinson's severity. NAC also increased signals related to dopamine transporters by 4–9%. This is significant because dopamine, a brain chemical, is often low in people with Parkinson's. These findings suggest that NAC might support brain function by boosting glutathione, which helps protect brain cells from damage. No serious side effects were reported in these studies, making NAC a promising option for further exploration. ^{1 2 6 7 8}

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

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40988585/

N-acetylcysteine for Parkinson's disease: a translational ... Intravenous NAC raised brain glutathione levels; high-dose oral NAC reached CSF. Two open-label trials (n = 65), reported ~ 13% improvement in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162018/

Current trends and future prospects of N-acetylcysteine ... This reflects research on how NAC may slow the progression of Parkinson's disease by maintaining mitochondrial function, which shields ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02212678

Repeated-Dose Oral N-acetylcysteine for the Treatment of ... The investigators' hypothesis is that repeated oral dosing of NAC will result in increased brain and red blood cell GSH concentrations in individuals with ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/17582024.2025.2563489?src=

N-acetylcysteine for Parkinson's disease: a translational ... Two open-label trials (n = 65), reported ~ 13% improvement in UPDRS scores and 4–9% dopamine transporter signal increases over three months. No serious adverse ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0157602

N-Acetyl Cysteine May Support Dopamine Neurons in ... The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5762253/

Repeated-dose Oral N-acetylcysteine in Parkinson Disease Recent controlled, clinical trials used NAC doses of 1200 to 8000 mg/day given from 4 weeks to 6 months with no reported major safety concerns.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1658361225000496

Current trends and future prospects of N-acetylcysteine ... More recently, NAC increases dopamine release and prevents degeneration of dopaminergic neurons to improve motor deficits in animal models of Parkinson.

8. tandfonline.com tandfonline.com/doi/full/10.1080/01616412.2024.2325312

Full article: N-acetylcysteine increases dopamine release ... In addition, although NAC treatment is considered to be safe and without obvious side effects, there are risks associated with NAC overdoses [Citation43] or its ...