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

Multiple Myeloma Clinical Trial

Official title:

Randomized Controlled Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant (HCT) Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02420223
• Other study ID #: PRO00024391
• Status: Completed
• Phase: Phase 2
• Start date: July 17, 2015
• Est. completion date: February 2020

Study information

• Verified date: May 2021
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: February 2020
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma

Intervention

Drug:
• Propranolol

Locations

Country	Name	City	State
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (1)

Knight JM, Rizzo JD, Hari P, Pasquini MC, Giles KE, D'Souza A, Logan BR, Hamadani M, Chhabra S, Dhakal B, Shah N, Sriram D, Horowitz MM, Cole SW. Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker tria — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (Pre-Transplant); 4 weeks post-transplant
Secondary	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.	Baseline and 4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks after transplant
Secondary	Time (Days) to Platelet Engraftment	This measure is the mean time to the beginning of three consecutive days where the platelet count is at least 20,000/mm^3 (20 x 10^9/L) unsupported by a platelet transfusion.	4 weeks
Secondary	Number of Participants Diagnosed With Culture-positive Infection or Neutropenic Fever Greater Than 100.4 Degrees Fahrenheit	This measure is the number of subjects diagnosed with culture-positive infection or neutropenic fever greater than 100.4 degrees Fahrenheit.	Up to 100 days after transplant
Secondary	Number of Participants With Myeloma Response as a Function of Beta-blocker Administration	This measure is the number of participants experiencing a response defined by the International Uniform Response Criteria as: very good partial response (VGPR) or better (near complete response (nCR), complete response (CR), and stringent CR (sCR) according to at day 100 post-Hematopoietic Cell Transplant.	100 days after transplant