Parkinson's DiseasePhase 1NCT01427517
Intravenous N-acetylcysteine for the Treatment of Gaucher's Disease and Parkinson's Disease
A Phase 1 study testing N-acetylcysteine in people with Parkinson's Disease and Gaucher's Disease, run by University of Minnesota at 1 site in United States.
Trial summary
The investigators are interested in determining if the investigators are able to detect changes in brain chemistry using Magnetic Resonance Spectroscopy (MRS) in individuals with Parkinson's disease (PD), those with Gaucher's disease (GD), and those without neurological disorders (healthy controls) when they are given… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease, Gaucher's Disease
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Dec 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All participants must be 18 years or older.
- All enrollees must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent.
- Individuals with medically stable Parkinson's disease (in the opinion of the investigator).
- All participants must not have taken antioxidants coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study.
- Absence of dementia in all subjects, as determined by pre-scanning cognitive assessment.
- Control subjects who are able to undergo MRS
Who cannot join
- Inability to undergo MRI scanning without sedation
- Medically unstable conditions in any group as determined by the investigators
- Pregnant or lactating or those women of child-bearing age that are not using acceptable forms of contraception
- Diagnosis of asthma that is presently being treated with ANY medication, or past history of asthma/bronchospasm resulting in an emergency room visit, hospitalization or treatment
- Unable to adhere to study protocol for whatever reason
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
The investigators are interested in determining if the investigators are able to detect changes in brain chemistry using Magnetic Resonance Spectroscopy (MRS) in individuals with Parkinson's disease (PD), those with Gaucher's disease (GD), and those without neurological disorders (healthy controls) when they are given the antioxidant N-acetylcysteine (NAC). This study will combine information from a medical history, a physical examination and disease rating scales with results obtained using MRS brain scans and pharmacokinetic studies from blood samples. This research will require 1 visit that will require about 4 to 5 hours of time. During this study, participants will provide their medical history, be examined and undergo a rating scale for about one hour; the brain scan and pharmacokinetic studies will require 1.5-2 hours of time; in total the study will take about 4-5 hours.
Read the detailed description
Oxidative stress is implicated in the pathogenesis of a number of neurodegenerative diseases such as Parkinson's disease (PD). Further, levels of glutathione (GSH), a prevalent endogenous antioxidant, are decreased in the postmortem substantia nigra (SN) of individuals with PD, indicating increased oxidative stress, although this has yet not been confirmed in vivo. Increases in intracellular oxidative stress have also been observed in primary fibroblast cultures obtained from patients with GD, where enzyme replacement therapy resulted in increases in total GSH. The hypothesis that oxidative stress plays a key role in the neurodegeneration associated with PD suggests that antioxidants may be useful in altering disease progression.
N-acetylcysteine (NAC) is a well-known antioxidant that is thought to act both as a free radical scavenger and as a cysteine donor for the synthesis of GSH. NAC may be beneficial in the treatment of PD and GD. Magnetic resonance spectroscopy (MRS) methods may be able to determine if there are effects from NAC on central nervous system GSH levels. In addition, use of red blood cell (RBC) measurements of GSH, if correlated with brain concentrations, could serve as an easily measured biomarker to help characterize and monitor response to therapy. The investigators therefore propose to conduct a study of the effect of a single, intravenous dose of NAC on central (brain) measures of GSH and peripheral (RBC) measures of GSH in people with PD and healthy controls, through the use of simultaneous MRS techniques and pharmacokinetic studies. The investigators hypothesis and specific aims are as follows:
Hypothesis: RBC and brain GSH concentrations will increase following oral NAC administration in individuals with Parkinson's disease (PD), Gaucher's disease (GD), and control participants.
Specific Aims:
- Quantitate baseline plasma and red blood cell GSH concentrations in those with PD and GD and controls; and characterize NAC and GSH pharmacokinetics after a single intravenous NAC administration.
- Quantitate brain GSH levels (as ascertained through MRS) in those with PD and GD and controls at baseline and after a single intravenous NAC administration simultaneously with Aim 1.
- Construct a pharmacokinetic model to evaluate the relationship between peripheral (plasma and RBC) and central (brain) GSH measurements.
- Conditions
- Parkinson's Disease, Gaucher's Disease
- Being tested
- N-acetylcysteine
- Keywords
- Parkinson's disease, Gaucher's disease, Control
- Medical subject headings
- Parkinson Disease, Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC
Single, intravenous administration of N-acetylcysteine
| Study group | Role | What they receive |
|---|---|---|
| NAC in PD | Experimental | single intravenous administration of N-acetylcysteine in PD patients Receives: Drug: N-acetylcysteine |
| NAC in GD | Experimental | single intravenous administration of N-acetylcysteine in GD patients Receives: Drug: N-acetylcysteine |
| NAC in controls | Experimental | single intravenous administration of N-acetylcysteine in control subjects Receives: Drug: N-acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain GSH
change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects
Measured: Baseline and up to 110 minutes post-NAC administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2011 (estimated)
- Study startJul 2011
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Paul Tuite, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01427517
- Sponsor's protocol ID
- FWA00000312-2
- Other IDs
- U54NS065768
- Status last verified
- Oct 2019
- First submitted
- 30 Aug 2011
- Last updated
- 1 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G, Cloyd JC, Tuite PJ. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713.
PubMed 23860343
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous N-acetylcysteine for the Treatment of Gaucher's Disease and Parkinson's Disease
- ClinicalTrials.gov ID
- NCT01427517
- Acronym / sponsor ID
- FWA00000312-2
- Conditions
- Parkinson's Disease, Gaucher's Disease
- Keywords
- Parkinson's disease, Gaucher's disease, Control
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 1 Sep 2011 (estimated)
- Results
- Posted 2 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators are interested in determining if the investigators are able to detect changes in brain chemistry using Magnetic Resonance Spectroscopy (MRS) in individuals with Parkinson's disease (PD), those with Gaucher's disease (GD), and those without neurological disorders (healthy controls) when they are given the antioxidant N-acetylcysteine (NAC). This study will combine information from a medical history, a physical examination and disease rating scales with results obtained using MRS brain scans and pharmacokinetic studies from blood samples. This research will require 1 visit that will require about 4 to 5 hours of time. During this study, participants will provide their medical history, be examined and undergo a rating scale for about one hour; the brain scan and pharmacokinetic studies will require 1.5-2 hours of time; in total the study will take about 4-5 hours.
Detailed description
Oxidative stress is implicated in the pathogenesis of a number of neurodegenerative diseases such as Parkinson's disease (PD). Further, levels of glutathione (GSH), a prevalent endogenous antioxidant, are decreased in the postmortem substantia nigra (SN) of individuals with PD, indicating increased oxidative stress, although this has yet not been confirmed in vivo. Increases in intracellular oxidative stress have also been observed in primary fibroblast cultures obtained from patients with GD, where enzyme replacement therapy resulted in increases in total GSH. The hypothesis that oxidative stress plays a key role in the neurodegeneration associated with PD suggests that antioxidants may be useful in altering disease progression.
N-acetylcysteine (NAC) is a well-known antioxidant that is thought to act both as a free radical scavenger and as a cysteine donor for the synthesis of GSH. NAC may be beneficial in the treatment of PD and GD. Magnetic resonance spectroscopy (MRS) methods may be able to determine if there are effects from NAC on central nervous system GSH levels. In addition, use of red blood cell (RBC) measurements of GSH, if correlated with brain concentrations, could serve as an easily measured biomarker to help characterize and monitor response to therapy. The investigators therefore propose to conduct a study of the effect of a single, intravenous dose of NAC on central (brain) measures of GSH and peripheral (RBC) measures of GSH in people with PD and healthy controls, through the use of simultaneous MRS techniques and pharmacokinetic studies. The investigators hypothesis and specific aims are as follows:
Hypothesis: RBC and brain GSH concentrations will increase following oral NAC administration in individuals with Parkinson's disease (PD), Gaucher's disease (GD), and control participants.
Specific Aims:
- Quantitate baseline plasma and red blood cell GSH concentrations in those with PD and GD and controls; and characterize NAC and GSH pharmacokinetics after a single intravenous NAC administration.
- Quantitate brain GSH levels (as ascertained through MRS) in those with PD and GD and controls at baseline and after a single intravenous NAC administration simultaneously with Aim 1.
- Construct a pharmacokinetic model to evaluate the relationship between peripheral (plasma and RBC) and central (brain) GSH measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NAC in PD | Experimental | Drug: N-acetylcysteinesingle intravenous administration of N-acetylcysteine in PD patients |
| NAC in GD | Experimental | Drug: N-acetylcysteinesingle intravenous administration of N-acetylcysteine in GD patients |
| NAC in controls | Experimental | Drug: N-acetylcysteinesingle intravenous administration of N-acetylcysteine in control subjects |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- All participants must be 18 years or older.
- All enrollees must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent.
- Individuals with medically stable Parkinson's disease (in the opinion of the investigator).
- All participants must not have taken antioxidants coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study.
- Absence of dementia in all subjects, as determined by pre-scanning cognitive assessment.
Key exclusion criteria (5 listed)
- Inability to undergo MRI scanning without sedation
- Medically unstable conditions in any group as determined by the investigators
- Pregnant or lactating or those women of child-bearing age that are not using acceptable forms of contraception
- Diagnosis of asthma that is presently being treated with ANY medication, or past history of asthma/bronchospasm resulting in an emergency room visit, hospitalization or treatment
- Unable to adhere to study protocol for whatever reason
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NACSingle, intravenous administration of N-acetylcysteine | Drug | NAC in GD, NAC in PD, NAC in controls |
Primary outcome
Brain GSH
Time frame: Baseline and up to 110 minutes post-NAC administration
change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23860343Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G, Cloyd JC, Tuite PJ. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Tuite, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-acetylcysteine in people with Parkinson's Disease and Gaucher's Disease, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain GSH (time frame: Baseline and up to 110 minutes post-NAC administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01427517, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019; AzTrials last refreshed its copy on 8 Nov 2026.