Biomarker Assessments of Leukine During Treatment of Parkinson's Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03790670|
Recruitment Status : Recruiting
First Posted : January 2, 2019
Last Update Posted : October 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Drug: sargramostim||Phase 1|
Primary Objectives: There are three study goals. 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, the investigators 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 lowered dose was chosen based on known tolerability and parallel-linked immune reconstitution seen in cancer-associated disease treatments. Due to fragility of the patient population and prior recorded adverse events the proposed dose reductions are justified.
Over a course of 24 months, the 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 will be examined. Individual T cell parameters that include links between T cell function and subset analyses and clinical neurological signs and symptoms will be examined. These immune parameters will be serially examined as they may contribute to the immune deficits in PD. Thus, timed analyses of changes in T cell phenotypes and/or function will be completed. In addition, the investigators will assess the functional stability of the immune deficits in PD and will determine whether the immune deficits of PD are consistent during baseline data collection. The potential Leukine-induced motor control and mobility improvements will be determined by assessing UPDRS part I, II, III, and IV scores off treatment and on treatment. Specifically, over the course of this six-month treatment study, various biomarkers will be assessed including: T cell markers of immune activation, DNA methylation status, and B cell and bone marrow progenitor cell markers. We hope to uncover the time course of Treg induction, as well as link the pharmacokinetics of Leukine treatment (not previously recorded) to changes in specific biomarkers. Additionally, changes in the humoral response following extended Leukine treatment will be assessed by measuring the presence of antibodies against Leukine and alterations in B cell frequencies.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety, Tolerability and Biomarker Assessments of Leukine (Sargramostim) During Extended Timed Treatment for Parkinson's Disease: A Phase I Pilot Study|
|Actual Study Start Date :||January 30, 2019|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||December 30, 2022|
Experimental: Leukine Treatment
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)
Recombinant human GM-CSF produced by recombinant DNA technology using a yeast (S. cerevisiae) expression system
Other Name: Leukine
- Incidence of Treatment-Associated Adverse Events [ Time Frame: monthly during the course of treatment, up to 24 months, followed by 1 month drug cessation ]The safety of Leukine administration in PD will be examined by documenting abnormal results from CBC with differential, total T cell count, or comprehensive metabolic panel analyses; abnormal physical and or neurological exam findings; abnormal levels of antibodies to GM-CSF; clinically increasing Unified Parkinson's disease Rating Scale (UPDRS) part I, II, III, and IV scores as determined by the examining physician; and other adverse events. These safety assessments will be made every four weeks.
- Determination of Immune Cell Phenotype [ Time Frame: 24 months of treatment, followed by 1 month drug cessation ]Measurements will include change in CD45RO+ or FAS+ frequencies in CD4+ T cells; change in CD31+ frequencies in CD4+ T cells, Teff or Treg subsets; change in ItgB7+ frequencies in CD4+ T cells or the Teff subset; change in ItgB4B7+ frequencies in CD4+ T cells or the Treg subset; change in CD27+ frequencies in CD4+ T cells, Teff or Treg subsets, change in CCR7+ frequencies in CD4+ T cells, Teff or Treg subsets; change in FoxP3+ frequencies in CD4+ T cells, Teff or Treg subsets; change in CD34, CD117, or CD135 levels; change in DNA methylation status. The measurements will be combined to determine overall changes in immune cell frequency and T cell subset phenotype both on and off treatment.
- Determination of Immune Cell Number [ Time Frame: 24 months of treatment, followed by 1 month drug cessation ]Measurements will include changes in levels of lymphocytes or CD4+ T cells, as well as T cell, B cell, and bone marrow progenitor subsets.
- Determination of Immune Cell Function [ Time Frame: 24 months of treatment, followed by 1 month drug cessation ]Measurements will include changes in T cell function via proliferation and suppression assays and/or changes in B cell function via antibody production assessments.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03790670
|Contact: Katherine Olson, PhDemail@example.com|
|Contact: Melinda Wojtkiewicz, B.Sfirstname.lastname@example.org|
|Principal Investigator:||Howard Gendelman, MD||UNMC|