Physiological Effects of Nutritional Support in Patients With Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT02445651
• Recruitment Status: Active, not recruiting
• First Posted: May 15, 2015
• Last Update Posted: July 14, 2020
• Sponsor: Thomas Jefferson University
• Information provided by (Responsible Party): Thomas Jefferson University

Study Description

Brief Summary:

Parkinson's disease (PD) is a neurodegenerative disorder of unknown cause that affects more than a million Americans. It's most prominent pathology is the degeneration of dopaminergic neurons in the brain. It is believed that oxidative stress and inflammation play an important role in the pathophysiology of Parkinson's disease as well.

The object of this study is to evaluate whether nutritional supplementation with compounds that have been shown to have either anti- inflammatory, or antioxidant effects, might support brain function in patients with Parkinson's disease, particularly in regards to the dopamine system. Enrolled patients will be randomly assigned to receive oral and intravenous n-acetyl cysteine (NAC), or standard PD care. This study will utilize Ioflupane (DaTscan) single photon emission computed tomography (SPECT) to measure dopamine function, magnetic resonance spectroscopy (MRS) to measure inflammatory and oxidative stress markers, and neurological measures to assess clinical symptoms, in patients with PD. Subjects will receive a DaTSCAN and MRS initially and after completing the supplement or NAC regimen.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease; Idiopathic Parkinson Disease	Dietary Supplement: Intravenous and Oral n-acetyl cysteine	Not Applicable

Detailed Description:

The study consists of two arms. The first arm of this study will receive intravenous and oral NAC, which is a strong antioxidant that increases brain glutathione, which may be beneficial in PD. NAC, is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. It is a common over-the-counter supplement and also is available as an injectable pharmaceutical that protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some benefits to use of NAC, such as its potential to counteract intracellular damage that leads to dopaminergic neuron death. It also has the potential to reduce markers of oxidative damage, protect against dopamine cell death from MPTP toxicity, and to increase glutathione in blood, which might be useful in preventing oxidative damage in PD patients.The second arm will be a waitlist control receiving standard PD care. It should be noted that both arms will receive standard PD care which will be augmented with NAC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: This is an Open Label study. Randomization will occur via a 2:1 ratio of the NAC group and the waitlist control groups using the method of random permuted blocks with random block sizes without stratification. 28 subjects in the NAC arm and 14 subjects have been enrolled in the standard of care arm.
• Primary Purpose: Supportive Care
• Official Title: Physiological Effects of Nutritional Support in Patients With Parkinson's Disease
• Study Start Date: March 2014
• Estimated Primary Completion Date: December 6, 2021
• Estimated Study Completion Date: December 6, 2021

Arms and Interventions

Arm	Intervention/treatment
Oral and IV N acetyl Cysteine Cohort; Administration of Intravenous (IV) and Oral N-acetyl Cysteine (NAC) Intervention: IV NAC infusion: Dose: 50mg in 200ml of D5W, frequency: over one hour 1 x per week for 90 days ± 30 days AND Oral N-acetyl Cysteine - one 600 mg tablet 2 x per day (on days IV N-acetyl cysteine is not administered)	Dietary Supplement: Intravenous and Oral n-acetyl cysteine
No Intervention: Control Cohort; Standard of Care Treatment

Outcome Measures

Primary Outcome Measures :

1. Changes in the dopamine transporter (DAT) which reflects the overall health of the dopaminergic system [ Time Frame: Baseline and 90 ± 30 days ]
   Single Photon Emission Computed Tomography (SPECT) Imaging (DaTScan) of Dopamine Uptake

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical Diagnosis of Parkinson's disease
• Subject is between 30 - 80 years of age
• Subject has a Hoehn and Yahr score of I - II inclusive
• Subject is on stable or on antiparkinsonian medication for at least a month
• Women of Childbearing potential will confirm a negative pregnancy test

Exclusion Criteria:

• Subject is allergic to iodine, cobalt, or any of the supplements that will be given in the study
• Subject has had previous brain surgery
• Subject has a score of 25 or less on Mini-Mental Status examination
• Subject is wheelchair-bound or bed-ridden; non ambulatory
• Subject has intracranial abnormalities that may complicate interpretation of the brain scans(e.g., stroke, tumor, vascular abnormality affecting the target area)
• Subject has a history of head trauma with loss of consciousness greater than 48 hours
• Subject has any medical disorder or physical condition that could reasonably be expected to interfere with the assessment of parkinsonian syndrome symptoms, or with any of the study assessments including the SPECT imaging.
• Subject has evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study
• Subject has a current alcohol or drug abuse
• Subject is pregnant or lactating
• Subject is enrolled in active clinical (drug or device) trial within the prior 30 days
• Subject is pending surgery during the course of the study
• History of very low blood pressure
• History of thrombocytopenia or clotting disorders
• Cancer patients receiving active chemotherapy
• History of active gallstone problems or a bile duct obstruction
• History of uncontrolled diabetes, asthma, gastroesophageal reflex disease, or thyroid
• History of severe kidney disease (if the patient reports this problem, a serum creatinine will be checked to assess GFR; if it is less than 30, the patient will be excluded)
• History of Leber's disease, a hereditary eye disease
• History of uncontrolled hypercalcemia
• History of active sarcoidosis, histoplasmosis, or lymphoma
• Patients taking medication that might interact with the supplements involved in this study will be evaluated on a case-by-case basis by PI study physician

Contacts and Locations

Locations

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Thomas Jefferson University

Investigators

• Principal Investigator: Daniel A Monti, MD,MBA; Thomas Jefferson University

  Study Documents (Full-Text)

Documents provided by Thomas Jefferson University:

Study Protocol and Statistical Analysis Plan: Study Protocol and Statistical Analysis Plan  [PDF] August 29, 2019

Study Protocol and Statistical Analysis Plan: Cover Page IRB approval August 29, 2019 to August 28, 2020  [PDF] August 29, 2019

More Information

Publications:

Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Cai J, Wei X, Bazzan AJ, Zhong L, Bowen B, Intenzo CM, Iacovitti L, Newberg AB. N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data. PLoS One. 2016 Jun 16;11(6):e0157602. doi: 10.1371/journal.pone.0157602. eCollection 2016.

• Responsible Party: Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT02445651
• Other Study ID Numbers: 14D.141
• First Posted: May 15, 2015
• Last Update Posted: July 14, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: After each participant completes the study, study scan data will be shared with co-investigators; participants may receive a copy of each scan after study completion.
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Study scan report will be offer to the subject after subject completes study
• Access Criteria: Authorized research personnel

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Thomas Jefferson University:

Integrative Medicine; Alternative Medicine; Complementary Medicine; Parkinson's disease; Neurodegenerative Diseases; Idiopathic Parkinson's disease; Single Photon Emission Computed Tomography (SPECT); Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Brain Diseases; Oral supplements; N-acetyl cysteine

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes