Healthy Subjects
Conditions
Keywords
Mellaril, Thioridazine, CD34+, Stem cells, Progenitor cells, Peripheral blood, mobilization, circulation
Brief summary
This study will investigate the possibility of using the drug thioridazine (also called Mellaril) to increase the number of certain types of cells moving from the bone marrow to the circulation in a group of healthy humans. The types of cells we hope to collect are called CD34+ progenitor, or stem cells. These cells can be used in the laboratory to better understand a number of diseases and suggest new strategies for therapy. Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies, as a renewable source of replacement cells and tissues to treat diseases including Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.
Detailed description
This is a single-arm, feasibility study to test whether a single dose of Mellaril (thioridazine HCL) is able to effectively mobilize CD34+ cells in a set of health human subjects. This study does not involve the use of placebos, and subjects will serve as their own controls for CD34+ cell mobilization. We hypothesize that a single dose of Mellaril (thioridazine HCL) will mobilize CD34+ progenitor cells into human peripheral blood by a factor of at least 10 fold, from 4 to 40 cells/microliter.
Interventions
DRUGMellaril
Subjects will undergo a physical exam including an electrocardiogram (EKG) and have blood drawn before treatment. A single 50 gm dose of thioridazine (Mellaril) will be given to eligible subjects. A second blood draw will occur at 24 hours post-treatment.
Sponsors
Oxnard Foundation
New Mexico Cancer Research Alliance
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy, non-smoking subjects (male or female) * Age: 18 to 55 years * All subjects must agree to refrain from consuming alcohol during for 48 hours after taking thioridazine. * Performance status Karnofsky score of 100%. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A female of child-bearing potential is any woman (regardless of sexual orientation, having not undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). * Ability to understand the purpose and procedures of this study, and the willingness to sign a written informed consent document. * Only subjects whose laboratory testing, including platelet counts and transaminase levels are within normal limits are eligible. * Subjects must pass pre-treatment screening by EKG to rule out long QT syndrome or subclinical cardiac arrhythmia.
Exclusion criteria
* Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Agent(s) or other agents used in study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, a febrile illness within 35 days of study entry, or psychiatric illness or dementia, or social situations that would limit compliance with study requirements. * Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. * Concomitant use of phenytoin excludes potential subjects from participation. * Subjects with known long QT syndrome or known history of cardiac arrhythmias are excluded from participation. * Subjects taking drugs known to inhibit P450 CYP2D6 are excluded from participation. * Subjects who received an investigational agent within 28 days of dosing with thioridazine on this protocol are excluded from participation. * Subjects who received thioridazine within 7 days of dosing on this protocol are excluded from participation. * Subjects who have had pelvic radiation are excluded from participation. * Subjects who have received myeloablative regimens at any time are excluded from participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CD34+ Progenitor Cell Mobilization | 8 hours following treatment | To measure CD34+ cells, a peripheral blood draw is taken from the enrolled subject at hour zero on day one of the study before treatment with oral thioridazine. Following treatment, blood draws are taken at 2, 4, 8 and 24 hours. These blood samples are analyzed using Clinical Laboratory Improvement Amendments (CLIA)-approved flow cytometry for CD34+ cell content. CD34+ cell levels will be reported as a percentage of total white blood cells (WBC) in the blood specimens and the difference between baseline and 8 hours will be reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | Up to 1 month after treatment | Toxicity will be evaluated according to the grading system (0-5) NCI CTCAE (Common Terminology Criteria for Adverse Events) version 4. Any subject who receives treatment on this protocol will be evaluable for toxicity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mellaril (Thioridazine) A single 50 gm dose of thioridizine (Mellaril) will be given orally at the beginning of the study
Mellaril: Subjects will undergo a physical exam including an electrocardiogram (EKG) and have blood drawn before treatment. A single 50 gm dose of thioridazine (Mellaril) will be given to eligible subjects. A second blood draw will occur at 24 hours post-treatment. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Mellaril (Thioridazine) |
|---|---|
| Age, Continuous | 34 years |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
CD34+ Progenitor Cell Mobilization
To measure CD34+ cells, a peripheral blood draw is taken from the enrolled subject at hour zero on day one of the study before treatment with oral thioridazine. Following treatment, blood draws are taken at 2, 4, 8 and 24 hours. These blood samples are analyzed using Clinical Laboratory Improvement Amendments (CLIA)-approved flow cytometry for CD34+ cell content. CD34+ cell levels will be reported as a percentage of total white blood cells (WBC) in the blood specimens and the difference between baseline and 8 hours will be reported
Time frame: 8 hours following treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mellaril (Thioridazine) | CD34+ Progenitor Cell Mobilization | CD34+ cells at baseline | 0.05 percentage of total WBC count | Standard Deviation 0.015 |
| Mellaril (Thioridazine) | CD34+ Progenitor Cell Mobilization | CD34+ cells at 8 hours | 0.05 percentage of total WBC count | Standard Deviation 0.018 |
| Mellaril (Thioridazine) | CD34+ Progenitor Cell Mobilization | Difference between baseline and 8 hours | 0 percentage of total WBC count | Standard Deviation 0.011 |
Secondary
Toxicity
Toxicity will be evaluated according to the grading system (0-5) NCI CTCAE (Common Terminology Criteria for Adverse Events) version 4. Any subject who receives treatment on this protocol will be evaluable for toxicity.
Time frame: Up to 1 month after treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mellaril (Thioridazine) | Toxicity | Grade 1 somnolence | 4 participants |
| Mellaril (Thioridazine) | Toxicity | Returned to baseline within 24 hours | 4 participants |