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Study of Urate Elevation in Parkinson's Disease, Phase 3 (SURE-PD3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Massachusetts General Hospital
The Parkinson Study Group
Michael J. Fox Foundation for Parkinson's Research
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Michael Alan Schwarzschild, Massachusetts General Hospital Identifier:
First received: December 19, 2015
Last updated: September 27, 2016
Last verified: September 2016

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial to determine whether oral inosine dosed to moderately elevate serum urate (from ≤5.7 mg/dL to 7.1-8.0 mg/dL) over 2 years slows clinical decline in early PD.

Clinical decline will be assessed as change in the primary outcome variable of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a composite scale comprising patient- and clinician-reported outcomes.

Condition Intervention Phase
Parkinson's Disease
Drug: Inosine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Randomized, Double-blind, Placebo-controlled Trial of Urate-elevating Inosine Treatment to Slow Clinical Decline in Early Parkinson's Disease

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Rate of clinical decline [ Time Frame: two years ] [ Designated as safety issue: No ]
    The primary outcome of the trial is rate of change in MDS-UPDRS I-III total score over 24 months estimated from a shared-baseline, random-slopes mixed model, censoring follow-up of subjects after initiation of dopaminergic therapy.

Secondary Outcome Measures:
  • Rate of developing adverse effects [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Safety also will be evaluated by comparing active vs. placebo treatment with respect to overall adverse event (AE) and serious AE (SAE) rate.

  • Proportion developing adverse effects [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Safety of oral inosine titrated to elevate trough serum urate to 7.1 - 8.0 mg/dL will be evaluated by comparing active vs. placebo treatment with respect to proportions of subjects experiencing individual types of AE, as classified by Medical Dictionary for Regulatory Activities (MedDRA) preferred term and system organ class.

  • Proportion of subjects tolerant of the treatment [ Time Frame: three months; two years ] [ Designated as safety issue: Yes ]
    Tolerability of a treatment will be defined as a proportion of all subjects in a treatment group who are tolerant of the treatment at 12 weeks (short-term tolerability) and 24 months (long-term tolerability). A subject who is tolerant of treatment will be defined as one who remains on-study and on the assigned treatment without one or more dose reductions lasting more than 4 weeks cumulative due to AEs. A treatment will be declared tolerable if the proportion who are tolerant is significantly greater than 50% by one-tailed testing at p < 0.05.

  • Time to disability warranting dopaminergic therapy [ Time Frame: two years ] [ Designated as safety issue: No ]
    Secondary efficacy outcomes will include time from baseline visit to disability warranting the initiation of dopaminergic therapy in each treatment group.

  • Clinical efficacy: Rate of change in PDQ-39 [ Time Frame: two years ] [ Designated as safety issue: No ]
    Rate of change in PDQ-39 scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group.

  • Clinical efficacy: Rate of change in Neuro-QOL [ Time Frame: two years ] [ Designated as safety issue: No ]
    Rate of change in Neuro-QOL scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group.

  • Clinical efficacy: Rate of change in Neuro-QOL depression module [ Time Frame: two years ] [ Designated as safety issue: No ]
    Rate of change in Neuro-QOL depression module scale points (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group.

  • Clinical efficacy: Rate of change in Schwab and England scale [ Time Frame: two years ] [ Designated as safety issue: No ]
    Rate of change in percentage points on the Schwab and England scale for functional disability (over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group.

  • Clinical efficacy: Rate of change in Montreal Cognitive Assessment (MoCA) [ Time Frame: two years ] [ Designated as safety issue: No ]
    Rate of change in points on the MoCA scale (for cognition; over the time between baseline visit and final visit on study drug) will be assessed for subjects in each treatment group.

  • Clinical efficacy: Proportion of subjects having developed disability warranting dopaminergic therapy [ Time Frame: up to 27 months ] [ Designated as safety issue: No ]
    Determinations of disability warranting initiation of dopaminergic therapy will be made every three months during period 1 (24 months on study drug) and monthly during period 2 (following study drug discontinuation, between months 24 and 27) for subjects who have not previously reached this level of disability. Analysis of measures that are equally evaluable at the end of both periods (such as proportion of subjects having developed disability warranting dopaminergic therapy), will be conducted as a three-part test: a) of significantly slower worsening during period 1, b) of non-inferior rates of worsening during period 2, and c) of a significant net benefit at the end of period 2. It could provide evidence of disease modification if all three evaluations were favorable.

  • Symptomatic effects [ Time Frame: three months (after both initiation and discontinuation of study drug) ] [ Designated as safety issue: No ]
    Symptomatic effects will be estimated by changes in motor and other features (e.g., as assess by short-term change in total MDS-UPDRS score) during the first 3 months of wash-in at the start of period 1 and during the 3-month wash-out of period 2.

Estimated Enrollment: 270
Study Start Date: June 2016
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inosine
Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.
Drug: Inosine
capsules containing 500 mg of inosine
Other Name: hypoxanthine 9-β-D-ribofuranoside
Placebo Comparator: Placebo
Placebo will be dosed to match the capsule titrations of the inosine group.
Drug: Placebo
capsules containing ~500 mg of lactose and appearing indistinguishable from inosine capsules
Other Name: inactive agent

Detailed Description:

Capsules containing 500 mg of inosine (active drug) or ~500 mg of lactose (placebo) will be taken orally up to two capsules three times per day (i.e., up to 3 g/day) for 24 months. In the inosine-treated group the number of capsules taken per day will be titrated to serum urate levels - measured at trough at study visits no more than three months apart - in order to achieve concentrations of 7.1-8.0 mg/dL. Initial dosing will be tailored to individualized factors including gender and pretreatment serum urate, and then advanced gradually toward the projected target dose. Adjustments in dosing of placebo capsules in the control arm will be algorithm-based to match dosing of inosine capsules in the active drug arm.

Following study drug discontinuation all subjects will be followed during a 3-month wash-out period by telephone calls and a final study visit. All study visits after screening will include measurement of the primary outcome variable (MDS-UPDRS) and most will include secondary outcome variables: adverse events, dose adjustments, disability warranting initiation of dopaminergic therapy, Quality of Life in Neurological Disorders (Neuro-QOL), 39-item Parkinson's Disease Questionnaire (PDQ-39), Schwab & England Activities of Daily Living (S&E ADL) scale, Montreal Cognitive Assessment (MoCA), and orthostatic vital signs.


Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


Study subjects meeting all of the following criteria will be allowed to enroll in the study:

  1. Willingness and ability to give written informed consent and to comply with trial procedures.
  2. Fulfillment of diagnostic criteria for idiopathic PD with at least two of the cardinal signs of PD (resting tremor, bradykinesia, rigidity) present at 2nd screening and baseline evaluations, as assessed by the Site Investigator.
  3. Absence of current or imminent (within 90 days of enrollment) PD disability requiring dopaminergic therapy, as assessed by the Site Investigator.
  4. Modified Hoehn and Yahr Scale Stage 1 to 2.5 inclusive.
  5. Age 30 or older at the time of PD diagnosis.
  6. Diagnosis of PD made within 3 years prior to 1st Screening Visit.
  7. Non-fasting serum urate ≤ 5.7 mg/dL at 1st Screening Visit (SC1).
  8. If the subject is female, then:

    1. Being surgically sterile (hysterectomy or tubal ligation), or
    2. Being postmenopausal (last menstruation was two years or more prior to 2nd Screening Visit), or
    3. For those of childbearing potential

      • Using a reliable form of contraception for 60 days or more prior to Baseline Visit and agreeing to continue such use for 30 days post last dose of study drug. Reliable forms of contraception include: abstinence; implanted, injected or oral contraceptives (birth control pills), intrauterine device in place for at least 3 months prior to Baseline Visit, vaginal ring with spermicide, barrier with spermicide such as male or female condom, diaphragm or cervical cap, transdermal patch; male partner with vasectomy.
      • And having a negative pregnancy test at the 2nd Screening Visit. [Note that a urine pregnancy test will be performed at screening on all women who are not at least two years postmenopausal or surgically sterile.]


Study subjects meeting any of the following criteria during screening evaluations will be excluded from entry into the study:

  1. Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
  2. Dopamine transporter (DAT) brain scan without evidence of dopamine deficit.
  3. History of gout.
  4. History of uric acid or urate urolithiasis, or recurrent urolithiasis all of unknown type.
  5. A screening test positive for uric acid crystalluria, urine pH ≤ 5.0, or an estimated glomerular filtration rate < 60 ml/min/1.73 m2.
  6. History of myocardial infarction or stroke.
  7. Symptomatic congestive heart failure with a documented ejection fraction below 45%.
  8. History of severe chronic obstructive pulmonary disease.
  9. Mini Mental State Exam score < 25; i.e., a score of 0 to 24.
  10. Use of any anti-parkinsonian medication (including levodopa, dopamine agonists, amantadine, entacapone and the anticholinergic agents trihexyphenidyl and benztropine) other than monoamine oxidase-B inhibitors within 60 days of Baseline, or in excess of 90 days.
  11. Change in the dosage of (or initiation of) a monoamine oxidase-B (MAO-B) inhibitor within 90 days prior to Baseline, i.e., entry on a MAO-B inhibitor requires a stable dosage for the 90 days prior to Baseline.
  12. Use of the following within 30 days prior to the Baseline Visit: inosine, allopurinol, febuxostat, probenecid, more than 50 IU of vitamin E daily, or more than 300 mg of vitamin C daily (though a daily standard multivitamin such as Bayer One-A-Day® or Centrum® is permissible), reserpine, methylphenidate, amphetamines, cinnarizine, monoamine oxidase-A inhibitors, tetrabenazine, neuroleptics or other dopamine blocking drugs.
  13. Use of the following within 90 days prior to the DAT neuroimaging screening evaluation: modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate, reserpine, or amphetamine derivative.
  14. Unstable dosing of a thiazide -- such as hydrochlorothiazide (e.g., Esidrex), chlorothiazide (e.g., Diuril), chlorthalidone (e.g., Hygroton), indapamide (e.g., Lozol), metolazone (e.g., Zaroxolyn), which are permissible as long as the subject is on a stable dose from 1 week prior to the 1st Screening Visit through the Baseline Visit.
  15. Known unstable medical or psychiatric condition that may compromise participation in the study. (Note that difficulty swallowing large capsules might preclude participation due to the size of the study drug capsules.)
  16. Clinically serious abnormality in the screening visit laboratory studies or ECG, as determined by the Site Investigator.
  17. Participation in another investigational treatment study within 30 days prior to the Baseline Visit.
  18. Known hypersensitivity or intolerability to inosine.
  19. Known hypersensitivity to DaTscan (either the active substance of ioflupane I-123 or to any of the excipients).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02642393

Contact: Sheehan F Wheeler 617-726-5714

  Hide Study Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Candace Cromer    205-996-4034   
United States, Arizona
Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Sanja Obradov    602-406-3719   
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Alisa Powell    480-301-8788   
Banner Sun Health Research Institute Recruiting
Sun City, Arizona, United States, 85351
Contact: Molly Goddard    623-832-5726   
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Cindy Lawrence    858-246-2537   
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Gina Barles    323-442-5723   
University of California Davis Recruiting
Sacramento, California, United States, 95817
Contact: Siobhan Vasquez    916-703-9105   
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Aaron Daley    415-476-9276   
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Nicola Haakonsen    303-724-4644    NICOLA.HAAKONSEN@UCDENVER.EDU   
Contact: Lindsay Hosford    303-724-6247   
Rocky Mountain Movement Disorder Center Recruiting
Englewood, Colorado, United States, 80113
Contact: Marinda Nelson    303-867-5471   
United States, Connecticut
Hartford HealthCare Movement Disorders Center Recruiting
Vernon, Connecticut, United States, 06066
Contact: Sheila Thurlow    860-870-6385   
United States, Florida
University of South Florida Recruiting
Tampa, Florida, United States, 33613
Contact: Claudia Rocha    813-396-0757   
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30329
Contact: Elaine Sperin    404-712-7044   
Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Buff Farrow    706-721-0619   
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Cynthia Poon    312-503-8216   
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Luci Blasucci    312-563-2900 ext 4 - SUREPD3   
Neurosciences Institute at Central DuPage Hospital Recruiting
Winfield, Illinois, United States, 60190
Contact: Komal Sharma    630-933-6844   
United States, Indiana
Indiana University Recruiting
Indianpolis, Indiana, United States, 46202
Contact: Andrea Hurt    317-963-7449   
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: April Langhammer    913-588-6989   
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Annette Robinson    502-540-3585   
United States, Louisiana
Oschner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Jamie Frank    504-842-5530   
United States, Maryland
University of Maryland, Baltimore Recruiting
Baltimore, Maryland, United States, 21201
Contact: Katherine Holmes    410-328-4892   
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Becky Dunlop    410-955-8795   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Grace Bwala    617-643-0654   
Boston University Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Raymond James    617-638-7745   
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Althea Silver    617-667-9885   
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Angela Stovall    734-647-4787   
Michigan State University Recruiting
East Lansing, Michigan, United States, 48824
Contact: Doozie Russell    517-884-2274   
Henry Ford Health System Recruiting
West Bloomfield, Michigan, United States, 48322
Contact: Patricia Kaminski    248-661-7257   
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Melissa Ammel    314-747-3470   
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Carolyn Peterson    402-552-2239   
United States, Nevada
Cleveland Clinic Lou Ruvo Center for Brain Health Recruiting
Las Vegas, Nevada, United States, 89106
Contact: Milagros Formoso    702-331-7049   
United States, New Jersey
Overlook Medical Center, Atlantic Neuroscience Institute Recruiting
Summit, New Jersey, United States, 07901
Contact: Diane Babek    908-598-7991   
United States, New York
Albany Medical College Recruiting
Albany, New York, United States, 12208
Contact: Darryl Collins    518-262-6651   
SUNY Downstate Medical Center Recruiting
Brooklyn, New York, United States, 11203
Contact: Sofya Glazman    718-270-7371   
Principal Investigator: Ivan Bodis-Wollner, MD         
Weill Cornell Medical Center Recruiting
New York City, New York, United States, 10021
Contact: Aneliya Hanineva    212-746-2474   
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Courtney Goodrich    315-464-6409   
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Contact: Lisa Gauger    919-668-1538   
United States, Ohio
University of Cincinnati/Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Erin Neefus    513-558-6555   
University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: David Korosec    216-844-1800   
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Yvette Pitchford    216-444-7513   
Ohio State University Recruiting
Columbus, Ohio, United States, 43221
Contact: Katherine Ambrogi    614-688-6685   
United States, Oregon
Oregon Health & Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Eric Serres    503-494-0276   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Devin Keating    215-829-7128   
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Sherri Mosovsky    412-692-4659   
United States, Rhode Island
Butler Hospital Recruiting
Providence, Rhode Island, United States, 02906
Contact: Courtney Bodge    401-455-6403   
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29403
Contact: Nancy Feracco    843-792-7859   
United States, Tennessee
University of Tennessee Health Science Center Recruiting
Memphis, Tennessee, United States, 38163
Contact: Amanda Nolte    901-448-7375   
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Dorothy Shearon    615-936-2025   
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9036
Contact: LaMetria West    214-648-5608   
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Christine Hunter    713-798-3951   
University of Texas Houston Medical School Recruiting
Houston, Texas, United States, 77030
Contact: Vicki Ephron    713-500-7073   
Baylor Scott & White Health Recruiting
Temple, Texas, United States, 76508
Contact: Melissa Ainslie    254-724-5679   
United States, Vermont
The University of Vermont Recruiting
Burlington, Vermont, United States, 05405
Contact: Emily Houston    802-656-8974   
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Katie Sullivan    434-982-6599   
VCU Parkinson's & Movement Disorder Center (McGuire Veterans Hospital) Recruiting
Richmond, Virginia, United States, 23230
Contact: Ginger Norris    804-662-5307   
Sentara Neurology Specialists Recruiting
Virginia Beach, Virginia, United States, 23456
Contact: Lisa Richardson    757-507-0642   
United States, Washington
Northwest Neurological PLLC Recruiting
Spokane, Washington, United States, 99202
Contact: Patty Dykstra    509-353-3710 ext 1   
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Lynn Wheeler    414-805-9307   
Sponsors and Collaborators
Michael Alan Schwarzschild
The Parkinson Study Group
Michael J. Fox Foundation for Parkinson's Research
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Study Chair: Michael A Schwarzschild, MD, PhD Massachusetts General Hospital (PI of Clinical Coordinating Center), PSG (Chair, SURE-PD3 Steering Committee)
Study Director: Alberto Ascherio, MD, DrPH Harvard School of Public Health, PSG (Co-Chair, SURE-PD3 Steering Committee)
Study Director: David Oakes, PhD University of Rochester (PI of Data Coordinating Center), PSG (Study Statistician/Member, SURE-PD3 Steering Committee)
Study Director: Eric A Macklin, PhD Massachusetts General Hospital, PSG (Study Statistician/Member, SURE-PD3 Steering Committee)
  More Information

Additional Information:
Responsible Party: Michael Alan Schwarzschild, Chair, SURE-PD3 Steering Committee, Massachusetts General Hospital Identifier: NCT02642393     History of Changes
Other Study ID Numbers: INO-PD-P3-2014  1U01NS090259-01A1 
Study First Received: December 19, 2015
Last Updated: September 27, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: De-identified data; per policies of NIH/NINDS and the PSG (Parkinson Study Group)

Keywords provided by Massachusetts General Hospital:
Parkinson's disease
Parkinson Study Group (PSG)

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Uric Acid
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs processed this record on September 29, 2016