Phase IIb Study of Intranasal Glutathione in Parkinson's Disease
Phase IIb Study of Intranasal Glutathione in Parkinson's Disease
Glutathione is an important nutrient for brain function and loss of glutathione has been
 implicated in Parkinson's disease. Glutathione is an antioxidant made in the body out of
 three amino acids, the nutrients that make up protein. This study will determine whether
 administration of either dose of glutathione, as a nasal spray, improves PD symptoms over
 time in a population of individuals with Parkinson's disease (PD).
The study begins with a pre-screening telephone interview. During this conversation
 participants will be asked a series of questions that will help us identify whether they are
 eligible for participation in this study. The pre-screening interview process will take
 approximately 10 minutes and will include all screening criteria that does not require
 clinical or laboratory examination

 All routine research visits will take place at Bastyr University Campus (Kenmore, WA).
 Participants will be asked to schedule visits at approximately the same time of day each
 visit .If they are on medications, we would like them to take their medications as they
 normally would on the day of the visit. Participants will be randomly assigned to one of
 three different study groups- a low dose group, a high dose group, or a placebo group.

 Study participants will invited to volunteer for two magnetic resonance imagine (MRI) scans
 as part of this study, an optional part of study participation. For those who volunteer and
 qualify, MRIs will be performed at the University of Washington Radiology Department early in
 the morning. One scan will be taken at baseline before taking glutathione and the second upon
 completion of the study medication. There will be a separate consent form for those who
 participate in the imaging portion of this study. Among the participants who volunteer, the
 first 15 to qualify for an MRI scan will be scheduled according to MRI availability.

 If participants are enrolled in the study, they will be asked to keep a daily log of actual
 frequency of administration of study medication, if any, as well as any changes in their PD
 symptoms, any adverse events they might experience, and their general well-being. We are
 giving participants enough medication to last four weeks, until the date of their next
 appointment. The medication should be taken three times a day (morning, afternoon, and
 evening).

 Visit 1- Baseline: (Approximately 1 hour)

 -  Urine sample

 -  Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..

 -  Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS),
 which involves assessing degree of tremor, ability to walk across the room, questions
 about ability to function independently (i.e. button your own shirt, feed yourself), and
 questions about mental health, including depression and intellectual impairment.

 -  Participant will be taught how and when to administer the study medication and be given
 a 1-month supply.

 Visit 2- Week 4 follow-up: (Approximately 1 hour)

 -  Urine sample

 -  Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..

 -  Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) and
 Webster-Step Second test involve assessing degree of tremor, ability to walk across the
 room, questions about ability to function independently (i.e. button your own shirt,
 feed yourself), and questions about mental health, including depression and intellectual
 impairment.

 -  Participant will be asked to return any unused study medication and applicator tips from
 the first month of the study and be given the next 1-month supply.

 -  We will inquire about medication changes and collect medication use logs.

 Visit 3- Week 8 follow-up: (Approximately 1/2 hour)

 -  Participant will be asked to return any unused study medication from the second month of
 the study and be given the next 1-month supply.

 -  We will inquire about medication changes and collect medication use logs.

 Visit 4- Week 12 follow-up: (Approximately 1 hour)

 -  Urine sample

 -  Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..

 -  Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) to
 assess degree of tremor, ability to walk across the room, questions about ability to
 function independently (i.e. button your own shirt, feed yourself), and questions about
 mental health, including depression and intellectual impairment.

 -  Participants will be asked to return any unused study medication from the third month of
 the study.

 -  We will inquire about medication changes and collect medication use logs.

 Visit 5- Week 16 follow-up: (Approximately 1 hour)

 This visit is included to determine whether there are any lasting effects of the study
 medication one month following discontinuation of use. The visit will include:

 -  Urine sample

 -  Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..

 -  Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS)
 which involves assessing degree of tremor, ability to walk across the room, questions
 about ability to function independently (i.e. button your own shirt, feed yourself), and
 questions about mental health, including depression and intellectual impairment.

 Overall, approximately 5 hours will be required for study participation. Blood draws will
 occur at most, but not all visits, and will not exceed 4 Tbsp per month.
Inclusion Criteria:

 -  Diagnosis of PD made by a clinical neurologist within the previous 10 years

 -  A modified Hoehn & Yahr Stage <3

 -  Age >21

 -  Subjects must be able to attend study visits at baseline, weeks 4, 8, 12, and 16.

 -  Subjects must be able to demonstrate, or have a caregiver administer, medication.

 -  Dose and frequency of pharmaceutical medications must be stable for 1 month prior to
 enrollment.

 -  Dose and frequency of naturopathic medications must be stable for 1 month prior to
 enrollment.

 -  Diet, exercise, and medications must be kept constant throughout participation in the
 study. (Medication changes considered essential by a participant's physician will be
 permitted and recorded).

 -  Ability to read and speak English.

 -  MRI cohort: Additional inclusion criteria specific to MRI.

 Exclusion Criteria:

 -  Dementia as evidenced by a Montreal Cognitive Assessment score of less than 24.

 -  Diseases with features common to PD (e.g., essential tremor, multiple system atrophy,
 progressive supranuclear palsy)

 -  Epilepsy

 -  A history of stroke

 -  The presence of other serious illnesses

 -  Respiratory disease (e.g. asthma, COPD)

 -  A history of brain surgery

 -  A history of structural brain disease

 -  A history of intranasal telangiectasia

 -  Supplementation with glutathione, and agents shown to increase glutathione, will not
 be permitted and their use will necessitate a 90-day washout period; this will be
 required for all forms of glutathione and the glutathione precursor, N-acetylcysteine.

 -  Pregnant or at risk of becoming pregnant (i.e., unwilling to use birth control if a
 sexually active, pre-menopausal female). Urine pregnancy tests will be administered to
 pre-menopausal women.

 -  MRI cohort: Additional exclusion criteria specific to MRI.