Pilot Study Using Propranolol To Promote Prenylation Of Gtpase Rap1b In Hematopoietic Stem Cell Transplant Recipients

NCT02535182 | Completed

• 1 other identifier: 24391
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a an ancillary study designed to explore whether an additional cell signaling pathway (prenylation of Rap1) that was recently identified as being under beta-adrenergic control may be affected by beta-blocker use.

Conditions

Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Prenylation levels in response to propranolol in a population of patients undergoing autologous hematopoietic stem cell transplantation

  Level of prenylation will be compared between patients exposed vs. not exposed to propranolol from 1-3 weeks before to 4 weeks following transplantation.

  1 year

Study Arms (2)

Control Arm

Patients who participate as controls on the main study will be controls on this ancillary study. The control arm will have blood drawn at baseline, day -2 and day -28 for the Rap1 testing.

Other: Blood Draw

Propranolol Arm

Patients who participate on the propranolol arm on the main study will be on the propranolol arm on this ancillary study. The propranolol arm will have blood drawn at baseline, day -2 and day -28 for the Rap1 testing.

Other: Blood Draw

Interventions

Blood Draw OTHER

Lab will draw one tube of blood to be stored in 8 mL Becton Dickinson (BD) Vacutainer Cell Preparation Tube (CPT) tubes at three study time points as described in Table 4.7b. These time points include baseline, Day -2 (immediately prior to transplant, central line placement, or administration of any conditioning regimen), and Day +28. Peripheral blood mononuclear cells (PBMCs) will be isolated from the whole blood samples collected from patients at the three designated time points (Baseline, Day -2, and Day +28). The lab will conduct western blotting on the cytosolic and membrane fractions of isolated PBMCs to determine the distribution of Rap1 in the different fractions, and the status of Rap1 prenylation in the cells.

Control Arm; Propranolol Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who are enrolled in the parent study (NCT02420223) are eligible for this ancillary study.

You may qualify if:

• Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:
• years of age
• ≤ 1 year since initiation of systemic anti-myeloma therapy
• Patient is scheduled for autologous hematopoietic stem cell transplant as the upfront therapy for their multiple myeloma
• Karnofsky Performance Status of ≥90 %; patients eligible for HCT are eligible for the study
• All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

You may not qualify if:

• Prior autologous HCT
• Non secretory multiple myeloma
• Concurrent beta-blocker therapy at or within 3 weeks of study entry.
• Previous intolerance to beta-blocker therapy
• Any medical contraindications to beta-blocker therapy including, but not limited to, symptomatic hypotension; drug hypersensitivity; sinus bradycardia, sick sinus syndrome, or 2nd or 3rd degree atrioventricular block without a pacemaker; uncompensated heart failure; or uncontrolled asthma
• Active, untreated depression screened for by the HCT physician (Patients who screen positive will be offered a referral to the MCW Psycho-Oncology program for further evaluation and treatment)
• Concurrent use of medications as specified in the protocol throughout the study or within one week of study entry.
• Pregnant or lactating women

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood mononuclear cells (PBMCs) will be isolated from the whole blood samples collected from patients at the three designated time points (Baseline, Day -2, and Day +28). Members of Dr. Carol Williams' laboratory (Professor, Pharmacology and Toxicology, MCW) will conduct western blotting on the cytosolic and membrane fractions of isolated PBMCs to determine the distribution of Rap1 in the different fractions, and the status of Rap1 prenylation in the cells.

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jennifer Knight, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: August 28, 2015
• Study Start: August 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: February 1, 2020
• Last Updated: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)