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

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ClinicalTrials.gov Identifier: NCT02420223
Recruitment Status : Active, not recruiting
First Posted : April 17, 2015
Last Update Posted : March 28, 2019
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
Jennifer M. Knight, Medical College of Wisconsin

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Propranolol Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Randomized Controlled Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant Recipients
Study Start Date : August 2015
Actual Primary Completion Date : July 2018
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: 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.
Drug: Propranolol
Other Name: Hemangeol, Inderal LA, Inderal XL, InnoPran XL, Inderal

No Intervention: Control Arm
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 6 total weeks for patient's on the control arm.



Primary Outcome Measures :
  1. Change in beta-adrenergically mediated gene expression following beta-blocker administration [ Time Frame: Change assessed from pre-transplant (Day -7) to day of transplant (Day 0) and from day of transplant to 4 weeks post-transplant (Beta-blocker administration starts Day -7 and continues through 4 weeks post-transplant) ]

Secondary Outcome Measures :
  1. Change in depression and anxiety as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
    Change will be assessed using the Hospital Anxiety and Depression Scale (HADS)

  2. Incidence of engraftment syndrome as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  3. Rates of neutrophil and platelet engraftment as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  4. Incidence of infection as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  5. Differences in myeloma response as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
    The trial will assess the rates of very good partial response (VGPR) or better (near complete response (nCR), CR, and stringent CR (sCR)) according to the International Uniform Response Criteria at day 100 post-HCT.

  6. Differences in treatment-related mortality as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  7. Differences in progression-free survival as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  8. Differences in overall survival as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]


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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
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): NCT02420223


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
University of California, Los Angeles
Investigators
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Principal Investigator: Jennifer Knight, MD Medical College of Wisconsin

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jennifer M. Knight, Assistant Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT02420223     History of Changes
Other Study ID Numbers: PRO00024391
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Keywords provided by Jennifer M. Knight, Medical College of Wisconsin:
Recipients
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Propranolol
Adrenergic Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents