Study of Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in HCT Recipients

Phase 2CompletedNCT02420223

Medical College of Wisconsin25 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

PropranololDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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 Medical College of Wisconsin 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

Locations (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Outcomes

Primary Outcomes

Beta-adrenergically Mediated Gene Expression (Change From Baseline)

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.

Time frame: Baseline (Pre-Transplant); 4 weeks post-transplant

Secondary Outcomes

Patient-reported Depression and Anxiety Scores

This measure will be assessed using the Hospital Anxiety and Depression Scale (HADS). The HADS scale includes fourteen 4-response Likert-scale questions graded 0 to 3. Seven questions are specific to depression; 7 questions are specific to anxiety. The score is the total of the responses in their respective categories. Lower scores indicated less depression and/or anxiety. Scores 0-7 indicate normal status; scores 8-10 suggest borderline abnormal status; and scores 11-21 indicate abnormal status. Only anxiety scores are presented.

Time frame: Baseline and 4 weeks

Number of Subjects Experiencing Engraftment Syndrome as a Function of Beta-blocker Administration

Number of subjects experiencing any of: fever, diarrhea or rash requiring steroid intervention within 48 hours before or after neutrophil recovery.

Time frame: 4 weeks

Time (Days) to Neutrophil Engraftment

This measure is the mean time to the beginning of three consecutive days where the neutrophil count (absolute neutrophil count) was 500 cells/mm\^3 (0.5 x 10\^9/L) or greater.

Time frame: 4 weeks after transplant

Time (Days) to Platelet Engraftment

Data from ClinicalTrials.gov

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