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Leukine (Sargramostim) for Parkinson's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Nebraska
Sponsor:
Collaborators:
Sanofi
UNeMed
Nebraska Neuroscience Alliance
Information provided by (Responsible Party):
Howard Gendelman, MD, University of Nebraska Medical Center
ClinicalTrials.gov Identifier:
NCT01882010
First received: June 13, 2013
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine if Leukine (sargramostim) can be safely administered to Parkinson's disease patients for an extended period of time (56 days) and restore immune deficits seen in Parkinson's patients compared to controls. The development of magnetoencephalography (MEG) as a monitoring tool for PD will also be explored. At enrollment and repeating again at two 4-week intervals, whole blood from PD patients and controls will be obtained for analyses and the results will be used to calculate immune response profiles as a baseline for comparison after drug treatment. Physical examinations and motor assessments will also be performed on PD patients. After the 8-week baseline data collection, control participation will end and drug treatment of PD patients will begin. PD patients will be randomized, and half will receive drug and half will receive placebo. Leukine at a dosage of 6 µg/kg or saline as placebo will be administered by subcutaneous injection daily for 56 days (8 weeks). During drug treatment, PD patients will be monitored every two weeks by physical examinations, motor assessments, and blood analyses. As follow-up, four weeks after drug administration has stopped, subjects will again have physical examinations, motor assessments, and blood analyses. MEG will be performed on PD patients and controls at the start of drug treatment, and on PD patients at the end of the drug treatment period and 4 weeks after drug is stopped.


Condition Intervention Phase
Parkinson's Disease
Procedure: blood draw
Procedure: physical exam and UPDRS part III assessment
Procedure: MEG
Drug: sargramostim
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Leukine (Sargramostim) for Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    An adverse event is defined as any undesirable physical, psychological, or behavioral effect experienced by a patient in conjunction with the use of the study drug.


Secondary Outcome Measures:
  • Change in UPDRS part III score [ Time Frame: 0, 4, 8, 10, 12, 14, 16, 20 weeks ] [ Designated as safety issue: Yes ]
    Score from part III motor examination of the Unified Parkinson's Disease Rating Scale Score Sheet.

  • Change in blood analyses results [ Time Frame: 0, 4, 8, 10, 12, 14, 16, 20 weeks ] [ Designated as safety issue: Yes ]
    Comprehensive metabolic panel, complete blood count with white blood cell differential (CBC/dif), and total T cell counts blood analyses

  • Abnormal findings in physical examination [ Time Frame: 0, 4, 8, 10, 12, 14, 16, 20 weeks ] [ Designated as safety issue: Yes ]
    Physical examination including temperature, blood pressure, pulse, and skin, lung, liver, heart, and abdomen assessments.

  • Change in FACS results [ Time Frame: 0, 4, 8, 10, 12, 14, 16, 20 weeks ] [ Designated as safety issue: No ]
    T cell markers analyzed by fluorescence-activated cell sorting.

  • Change in function of Treg cells [ Time Frame: 0, 4, 8, 10, 12, 14, 16, 20 weeks ] [ Designated as safety issue: No ]
    Regulatory T cells isolated from peripheral blood are tested for their ability to suppress proliferation of activated T cells.

  • Change in magnetoencephalography results [ Time Frame: 8, 16, 20 weeks ] [ Designated as safety issue: No ]
    Magnetoencephalography measurements during behavioral tasks


Estimated Enrollment: 32
Study Start Date: September 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Controls
Caregivers, spouse, friends, relatives of PD patients, have blood draws, MEG.
Procedure: blood draw
week 0
Procedure: blood draw
week 4
Procedure: blood draw
week 8
Procedure: MEG
week 8
Placebo Comparator: PD Patients placebo
PD patients that receive placebo, have blood draw, physical exam and UPDRS part III assessment, MEG.
Procedure: blood draw
week 0
Procedure: physical exam and UPDRS part III assessment
week 0
Procedure: blood draw
week 4
Procedure: physical exam and UPDRS part III assessment
week 4
Procedure: blood draw
week 8
Procedure: physical exam and UPDRS part III assessment
week 8
Procedure: MEG
week 8
Drug: placebo
saline solution daily subcutaneous injection 56 days
Other Name: saline solution
Procedure: blood draw
week 10
Procedure: physical exam and UPDRS part III assessment
week 10
Procedure: blood draw
week 12
Procedure: physical exam and UPDRS part III assessment
week 12
Procedure: blood draw
week 14
Procedure: physical exam and UPDRS part III assessment
week 14
Procedure: blood draw
week 16
Procedure: physical exam and UPDRS part III assessment
week 16
Procedure: MEG
week 16
Procedure: blood draw
week 20
Procedure: physical exam and UPDRS part III assessment
week 20
Procedure: MEG
week 20
Experimental: PD Patients sargramostim
PD patients that receive Leukine, have blood draw, physical exam and UPDRS part III assessment, MEG.
Procedure: blood draw
week 0
Procedure: physical exam and UPDRS part III assessment
week 0
Procedure: blood draw
week 4
Procedure: physical exam and UPDRS part III assessment
week 4
Procedure: blood draw
week 8
Procedure: physical exam and UPDRS part III assessment
week 8
Procedure: MEG
week 8
Drug: sargramostim

lyophilized 250 micrograms/vial

6 micrograms/kg daily subcutaneous injection

56 days

Other Name: Leukine
Procedure: blood draw
week 10
Procedure: physical exam and UPDRS part III assessment
week 10
Procedure: blood draw
week 12
Procedure: physical exam and UPDRS part III assessment
week 12
Procedure: blood draw
week 14
Procedure: physical exam and UPDRS part III assessment
week 14
Procedure: blood draw
week 16
Procedure: physical exam and UPDRS part III assessment
week 16
Procedure: MEG
week 16
Procedure: blood draw
week 20
Procedure: physical exam and UPDRS part III assessment
week 20
Procedure: MEG
week 20

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PD Patients

  • Onset of bradykinesia and 1 or both of the following: rest tremor and/or rigidity
  • Asymmetric onset of clinical signs
  • Progressive motor symptoms
  • Age at onset 35-85 years
  • Duration of PD symptoms of at least 3 years
  • Female subjects must be either:

Not pregnant, not breastfeeding, and not planning on becoming pregnant during the study; Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year and with follicle stimulating hormone (FSH) levels in the laboratory defined postmenopausal range, or has been surgically sterilized, or has had a hysterectomy at least 3 months prior to the start of this trial; or If of childbearing potential, must agree to use an effective method of avoiding pregnancy to the end of the trial and must have a negative serum beta-human chorionic gonadotropin (β-HCG) test. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap), abstinence, or a sterile sexual partner

  • Have the ability to comply with basic instructions and have the ability to sit still comfortably inside the MEG
  • Must be stage 4 or less according to the Hoehn and Yahr scale
  • Caregiver, spouse, friend, or relative must agree to participate in the research study

Control subjects:

  • Age 35-85 years
  • Caregiver, spouse, relative, or friend of eligible PD patient
  • Female subjects must be either:

Not pregnant, not breastfeeding, and not planning on becoming pregnant during the study; Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year and with follicle stimulating hormone (FSH) levels in the laboratory defined postmenopausal range, or has been surgically sterilized, or has had a hysterectomy at least 3 months prior to the start of this trial; or If of childbearing potential, must agree to use an effective method of avoiding pregnancy to the end of the trial and must have a negative serum beta-human chorionic gonadotropin (β-HCG) test. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap), abstinence, or a sterile sexual partner

  • Have the ability to comply with basic instructions and have the ability to sit still comfortably inside the MEG

Exclusion Criteria:

PD Patients

  • Atypical features indicative of a Parkinson-Plus disorder (Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD)) including cerebellar signs, supranuclear gaze palsy, apraxia and other cortical signs, or prominent autonomic failure
  • Neuroleptic treatment at time of onset of parkinsonism
  • Active treatment with a neuroleptic at time of study entry
  • History of repeated strokes with stepwise progression of parkinsonism
  • History of repeated head injury
  • History of definite encephalitis
  • More than one blood relative diagnosed with PD
  • Prominent gait imbalance early in the course (< 5 years)
  • Mini-mental state examination score <26
  • Hematological malignancy or coagulopathy
  • Abnormal blood analyses: hematocrit <30; WBC>11.5; clinically significant laboratory data (e.g. alanine aminotransferase [ALT] or aspartate aminotransferase [AST] 3x the upper limit of normal [ULN]), or any abnormal laboratory value that could interfere with the assessment of safety in the judgment of the investigator; significant abnormalities on the clinical examination, vital signs, and clinical chemistry or hematology results (excluding findings of Parkinson's disease), that may interfere with the study or present a safety risk for the subject as judged by the clinical investigator charged in the care of study participants
  • Serious medical illness or co-morbidity that may interfere with participation in the study
  • Brain surgery for parkinsonism (DBS, cell implantation, gene therapy)
  • History of an autoimmune disorder or systemic inflammatory disorder
  • Immunostimulatory or immunosuppressive treatment (including amphetamines or systemic corticosteroids) within 90 days
  • Exclusively unilateral parkinsonism for longer than 3 years
  • Known hypersensitivity to GM-CSF, yeast-derived products or benzyl alcohol
  • Current lithium treatment
  • Individuals who have ferrous metal implanted in their body other than fillings
  • Individuals with current diagnoses of alcohol or substance abuse/dependence
  • Anyone who is not appropriate for participation in this research protocol as deemed by the principal or co-investigator

Control subjects:

  • Positive response to more than 3 items on the PD Screening Questionnaire
  • More than one blood relative diagnosed with by PD
  • Mini-mental state examination score <26
  • Hematological malignancy or coagulopathy
  • Abnormal blood analyses: hematocrit <30; WBC>11.5; clinically significant laboratory data (e.g. alanine aminotransferase [ALT] or aspartate aminotransferase [AST] 3x the upper limit of normal [ULN]), or any abnormal laboratory value that could interfere with the assessment of safety in the judgment of the investigator; significant abnormalities on the clinical examination, vital signs, and clinical chemistry or hematology results that may interfere with the study or present a safety risk for the subject as judged by the investigator
  • Serious medical illness or comorbidity that may interfere with participation in the study
  • History of an autoimmune disorder or systemic inflammatory disorder
  • Immunostimulatory or immunosuppressive treatment (including amphetamines or systemic corticosteroids) within 90 days
  • Individuals who have ferrous metal implanted in their body other than fillings
  • Individuals with current diagnoses of alcohol or substance abuse/dependence
  • Anyone who is not appropriate for participation in this research protocol as deemed by the principal or co-investigator

PD Screening Questionnaire

  • Do you have trouble arising from a chair?
  • Is your handwriting smaller than it once was?
  • Do people tell you that your voice is softer than it once was?
  • Is your balance poor?
  • Do your feet ever seem to get stuck to the floor?
  • Do people tell you that your face seems less expressive than it once did?
  • Do your arms and legs shake?
  • Do you have trouble buttoning buttons?
  • Do you shuffle your feet and/or take tiny steps when you walk?
  • Has anyone ever told you that you have Parkinson's disease?
  • Have you ever taken levodopa or Sinemet?
  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 ClinicalTrials.gov identifier: NCT01882010

Contacts
Contact: Carolyn Peterson, RN, BSN 402-552-2239 cpeterson@nebraskamed.com
Contact: LuAnn Larson, RN, BSN 402-559-8555 llarson@unmc.edu

Locations
United States, Nebraska
Neurology Consultants of Nebraska PC Recruiting
Omaha, Nebraska, United States, 68131
Contact: Pamela M Santamaria, MD    402-552-2650    pamsantamaria@nebraskaneurology.com   
Contact: Carolyn Peterson, RN, BSN    402-552-2239    cpeterson@nebraskamed.com   
Principal Investigator: Pamela M Santamaria, MD         
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Carolyn Peterson, RN, BSN    402-552-2239    cpeterson@nebraskamed.com   
Principal Investigator: Howard E Gendelman, MD         
Sub-Investigator: John Bertoni, MD         
Sub-Investigator: Philip J Bierman, MD         
Sub-Investigator: Jane L Meza, PhD         
Sub-Investigator: R L Mosley, PhD         
Sub-Investigator: Tony Wilson, PhD         
Sub-Investigator: Diego Torres-Russotto, MD         
Sub-Investigator: Amy Hellman, MD         
Sponsors and Collaborators
Howard Gendelman, MD
Sanofi
UNeMed
Nebraska Neuroscience Alliance
Investigators
Principal Investigator: Howard E Gendelman, MD University of Nebraska
  More Information

Publications:

Responsible Party: Howard Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases;Chairman, Department of Pharmacology and Experimental Neuroscience;Director of the Center for Neurodegenerative Diseases, University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT01882010     History of Changes
Other Study ID Numbers: 487-12-FB, 2R01NS034239
Study First Received: June 13, 2013
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Nebraska:
Parkinson's disease
motor function
immune activation
T cells
CD4
GMCSF
leukine
sargramostim
magnetoencephalography

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders

ClinicalTrials.gov processed this record on November 25, 2014