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

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ClinicalTrials.gov Identifier: NCT02535182
Recruitment Status : Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Jennifer M. Knight, Medical College of Wisconsin

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.

Condition or disease Intervention/treatment
Hematopoietic Stem Cell Transplantation Other: Blood Draw

Detailed Description:
This is a proof of concept randomized controlled pilot study assessing whether prenylation and membrane localization of Rap1 in PBMCs can be altered in individuals undergoing autologous HCT for MM by administering a daily beta-blocker (propranolol) to 20 participants. Outcomes of patients on this clinical trial will be compared to 20 participants in a control arm.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Pilot Study Using Propranolol To Promote Prenylation Of The Gtpase Rap1b In Hematopoietic Stem Cell Transplant Recipients
Actual Study Start Date : August 2015
Actual Primary Completion Date : July 2018
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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

Lab will draw one tube of blood to be stored in 8 mL BD Vacutainer 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.


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

Lab will draw one tube of blood to be stored in 8 mL BD Vacutainer 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.





Primary Outcome Measures :
  1. Prenylation levels in response to propranolol in a population of patients undergoing autologous hematopoietic stem cell transplantation [ Time Frame: 1 year ]
    Level of prenylation will be compared between patients exposed vs. not exposed to propranolol from 1-3 weeks before to 4 weeks following transplantation.


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.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients who are enrolled in the parent study (NCT02420223) are eligible for this ancillary study.
Criteria

Inclusion Criteria:

Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:

  1. 18-75 years of age
  2. ≤ 1 year since initiation of systemic anti-myeloma therapy
  3. Patient is scheduled for autologous hematopoietic stem cell transplant as the upfront therapy for their multiple myeloma
  4. Karnofsky Performance Status of ≥90 %; patients eligible for HCT are eligible for the study
  5. All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

Exclusion Criteria:

  1. Prior autologous HCT
  2. Non secretory multiple myeloma
  3. Concurrent beta-blocker therapy at or within 3 weeks of study entry.
  4. Previous intolerance to beta-blocker therapy
  5. 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
  6. 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)
  7. Concurrent use of medications as specified in the protocol throughout the study or within one week of study entry.
  8. Pregnant or lactating women

Information from the National Library of Medicine

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): NCT02535182


Locations
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United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
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Principal Investigator: Jennifer Knight, MD Medical College of Wisconsin

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Responsible Party: Jennifer M. Knight, Assistant Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT02535182     History of Changes
Other Study ID Numbers: 24391
First Posted: August 28, 2015    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents