Randomized Controlled Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant (HCT) Recipients
Overview
- Phase
- Phase 2
- Intervention
- Propranolol
- Conditions
- Multiple Myeloma
- Sponsor
- Medical College of Wisconsin
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Beta-adrenergically Mediated Gene Expression (Change From Baseline)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a randomized controlled pilot study designed to evaluate whether the beta-adrenergic antagonist propranolol is effective in decreasing gene expression of stress-mediated beta-adrenergic pathways among a cohort of individuals receiving an autologous hematopoietic stem cell transplant (HCT) for multiple myeloma.
Detailed Description
This is a randomized controlled pilot study designed to evaluate whether a drug designed to block the physiologic effects of stress is effective at blocking stress-related gene expression in people receiving autologous stem cell transplants (their own cells) for multiple myeloma. Such stress-related gene expression is one way that the body is programmed to make specific proteins under conditions of stress. These proteins are believed to contribute to worse health outcomes. By using the drug propranolol, we aim to see whether we might block these negative health effects of stress as occur in the cancer setting and during the transplant process. We hypothesize that individuals taking propranolol will have more favorable gene expression. We will enroll 40 individuals, randomizing half to receive propranolol and half to serve as the control group not on the study drug. Study participants will start propranolol three weeks prior to their transplant and continue it until 30 days after the transplant. We will explore the effect of socioeconomic status, depression, and anxiety on individuals' gene expression response to propranolol with the idea that the more impoverished, anxious, or depressed individuals will display an even greater change in their gene expression. Part of the purpose of this study is also be to assess whether it is feasible to give this drug to individuals with cancer. Results of this study may inform larger trials assessing the effects of propranolol on cancer progression.
Investigators
Jennifer M. Knight
Assistant Professor
Medical College of Wisconsin
Eligibility Criteria
Inclusion Criteria
- •Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:
- •18-75 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.
Exclusion Criteria
- •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 Medical College of Wisconsin 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
Arms & Interventions
Propranolol
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Intervention: Propranolol
Outcomes
Primary Outcomes
Beta-adrenergically Mediated Gene Expression (Change From Baseline)
Time Frame: Baseline (Pre-Transplant); 4 weeks post-transplant
Expression (up or down regulation) of genes involved in the stress response can be modulated through the beta-adrenergic pathway. The log2 RNA abundance is a means to normalize results to determine whether a gene is up regulated (value greater than 1) or down regulated (value less than 1). Differential change in log2 RNA abundance is defined by the fold change (FC) as log2FC=Log2(B)-Log2(A). Logarithmic measures are unitless. The change in the measure between two time points determines whether a gene has up-or down-regulated.
Secondary Outcomes
- Number of Subjects Experiencing Engraftment Syndrome as a Function of Beta-blocker Administration(4 weeks)
- Time (Days) to Neutrophil Engraftment(4 weeks after transplant)
- Number of Participants With Myeloma Response as a Function of Beta-blocker Administration(100 days after transplant)
- Time (Days) to Platelet Engraftment(4 weeks)
- Number of Participants Diagnosed With Culture-positive Infection or Neutropenic Fever Greater Than 100.4 Degrees Fahrenheit(Up to 100 days after transplant)
- Patient-reported Depression and Anxiety Scores(Baseline and 4 weeks)