Feasibility of Thioridazine as a Mobilizing Agent for CD34+ Hematopoietic Progenitor Cells

NCT01765803 | Terminated Early Phase 1 Results DMC

• 1 other identifier: INST 1208
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Mellaril; Thioridazine; CD34+; Stem cells; Progenitor cells; Peripheral blood; mobilization; circulation

Outcome Measures

Primary Outcomes (1)

• 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

  8 hours following treatment

Secondary Outcomes (1)

• Toxicity

  Up to 1 month after treatment

Study Arms (1)

Mellaril (thioridazine)

EXPERIMENTAL

A single 50 gm dose of thioridizine (Mellaril) will be given orally at the beginning of the study

Drug: Mellaril

Interventions

Mellaril DRUG

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.

Also known as: Thioridazine

Mellaril (thioridazine)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead
• Oxnard Foundation: collaborator

Study Sites (1)

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

Related Links

• New Mexico Cancer Care Alliance
• UNM Cancer Center

MeSH Terms

Interventions

Thioridazine

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Stuart Winter, MD
• Organization: University of New Mexico

SWinter@salud.unm.edu

505-272-4461

Study Officials

• Stuart S Winter, MD

  University of New Mexico Health Sciences Center/Pediatric Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 10, 2013
• Study Start: June 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 14, 2016
• Results First Posted: July 20, 2015

Record last verified: 2016-03

Locations

US (1)