Clinical trial NCT03063242: Sargramostim for Myeloid Dendritic Cell Deficiency
Official title: Sargramostim to Reverse Myeloid Dendritic Cell Deficiency
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Diseases
Kidney Transplant
Keywords: Sargramostim
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2017-02-24
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Project I will be used to optimize the dosage and timing of sargramostim administration with regard to the primary and secondary outcomes. Thus, Project II and III treatment will only begin once all 5 Project I participants have completed treatment and the data have been analyzed to guide subsequent dosing
Primary purpose: TREATMENT

Brief summary: The study will determine whether administration of sargramostim will improve myeloid dendritic cell deficiency in various study groups, including healthy subjects and patients with chronic kidney disease, including those with kidney transplants.

Detailed description: The overall objective of this project is to study the ability of sargramostim to enhance mDC level and function, including subsequent stimulation of T cell responses, in various human subjects with demonstrated myeloid dendritic cell (mDC) and T cell deficiency.

Single center nonrandomized trial with an interrupted time series design involving measures on blood samples from three separate populations before and after administration of sargramostim.

The objective is to determine the safety and dose response of sargramostim administration in healthy participants and in patients with chronic kidney disease (CKD) and kidney transplants.

Additionally to determine whether reversal of mDC/T cell deficiency by sargramostim results in augmented T cell responses in these three groups.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years \< 80 years
* Absence of acute or chronic medical condition and taking no prescription medications (Project I)
* Stable native or transplant kidney function (Project II/III)

Exclusion Criteria:

* Age \< 18 or \> 80 years
* History of non-adherence to prescribed medications (Projects II and III)
* Active drug or heavy alcohol use (defined as \> 4 drinks/day)
* Pregnancy or breast feeding
* Active infection (bacterial or viral) or clinically significant infections within the past three months (e.g. those requiring hospitalization, or as judged by the PI, except for CMV viremia in Project III)
* Active malignancy (with the exception of excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or adequately treated pre-invasive cervical cancer in situ)
* Unstable cardiovascular status (angina, arrhythmias, congestive heart failure (CHF) etc...)
* History of liver disease (as defined by a diagnosis of uncompensated cirrhosis)
* History of lung disease (including moderate-severe Chronic Obstructive Pulmonary Disease (COPD), interstitial lung disease, or asthma)
* Known hypersensitivity to yeast-derived products
* Hemoglobin \< 10 g/dL and hematocrit \< 30%.
* Abnormal white blood cell count (WBC) count at baseline (\< 3 or \> 12 x 103 cells/mm3, except Project III)
* Treatment with WBC growth factors (G-CSF or GM-CSF) or immunosuppressive medications (tacrolimus, cyclosporine, mycophenolate, azathioprine, corticosteroids, chlorambucil, cyclophosphamide) within 4 weeks of study (erythropoiesis-stimulating agents will be allowed for Project II and immunosuppression for Project III)
* Treatment with lithium within 4 weeks of study
* History of arterial or venous thrombosis

Primary outcomes:
measure: Change in peripheral blood mDC levels
timeFrame: Baseline to 2 weeks
Secondary outcomes:
measure: Proportion of patients with adverse events during the intervention.
timeFrame: Baseline to 2 weeks
measure: Increase in T cell levels, mDC Interleukin (IL)-12 production, and interferon-gamma (IFN-y) production in QuantiFERON-CMV and QuantiFERON-Monitor assays after the intervention.
timeFrame: Baseline to 2 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Karl Womer, MD
role: PRINCIPAL_INVESTIGATOR
References: