Biomarker Assessments of Leukine During Treatment of Parkinson's Disease

• Status: Recruiting
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

Summary

First, the investigators will determine the safety of a 24 month regimen of Leukine administered as a weight-based dose at 3 µg/kg/day for 5 days (week), followed by a 2-day holiday (weekend). This 24 month (n=10) pilot study will extend the prior 2 month observation tests towards the goal of assessing the safety of Leukine for treatment of Parkinson's disease (PD). Clinical signs and symptoms will be measured by personal well-being, physical, and neurological examinations (UPDRS Parts I, II, III, and IV assessments) and blood tests (CBC with differential, total T cell count, and a comprehensive metabolic sera panel). Second, we will assess regimen tolerability administered in a dose reduction, from 6 µg/kg/day without interruption, to 3 µg/kg/day with 2 day drug holidays. The investigators will examine over a time of 24 months, effects of treatment on defined adaptive immune deficits in PD as measured by analysis of peripheral blood mononuclear cells collected before, during, and after cessation of Leukine administration. Individual T cell parameters will be assessed and will include links between T cell function and subset analyses and clinical neurological signs and symptoms. In addition, the functional stability of the immune deficits will be assess in PD by examining T cell subsets in PD patients in this study against prior results. The investigators will also determine whether the immune deficits of PD are consistent during baseline data collection, and the potential Leukine-induced motor control and mobility improvements will be determined by UPDRS part I, II, III, and IV scores off treatment and on treatment.

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

Details

• Lead Sponsor: University of Nebraska
• Treatments: Sargramostim

Criteria

Inclusion Criteria:

• 1. Onset of bradykinesia and 1 or both of the following: rest tremor and/or rigidity

2. Asymmetric onset of clinical signs

3. Progressive motor symptoms

4. Age at onset 35-85 years

5. Duration of PD symptoms of at least 3 years

6. Female subjects must be either:

1. Not pregnant, not breastfeeding, and not planning on becoming pregnant during the study;

2. 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

3. 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.

7. Must be stage 4 or less according to the Hoehn and Yahr scale

Exclusion Criteria:

• 1. 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

2. Neuroleptic treatment at time of onset of parkinsonism

3. Active treatment with a neuroleptic at time of study entry

4. History of repeated strokes with stepwise progression of parkinsonism

5. History of repeated head injury

6. History of definite encephalitis

7. More than one blood relative diagnosed with PD

8. Prominent gait imbalance early in the course (< 5 years)

9. Mini-mental state examination score <26

10. Hematological malignancy or coagulopathy

11. 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

12. Serious medical illness or co-morbidity that may interfere with participation in the study

13. Brain surgery for parkinsonism (DBS, cell implantation, gene therapy)

14. History of an autoimmune disorder or systemic inflammatory disorder deemed significant by physician

15. Immunostimulatory or immunosuppressive treatment (including amphet-amines or systemic corticosteroids) within 90 days

16. Exclusively unilateral parkinsonism for longer than 3 years

17. Known hypersensitivity to GM-CSF, yeast-derived products

18. Current lithium treatment

19. Individuals with current diagnoses of alcohol or substance abuse/dependence

20. Anyone who is not appropriate for participation in this research protocol as deemed by the principal or co-investigator

21. Anyone who has previously been treated with GM-CSF as an immunomodulatory therapy

22. Anyone with poor venous access