Leukine (Sargramostim) for Parkinson's Disease

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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. In addtion, at the second cohort of 8 PD subjects, we will evaluate the potential Leukine-induced motor control and mobility improvements. Also, levels of the neurotransmitters glutamate, glutamine, serotonin, acetylcholine, GABA, norepinephrine and epinephrine in serum/plasma will be analyzed to correlate with changes in motor function and drug treatment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Howard Gendelman, MD
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Nebraska Neuroscience Alliance; Sanofi; UNeMed
• Treatments: Sargramostim

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?