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| Name | Class |
|---|---|
| University of California, Los Angeles | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol | Experimental | 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. |
|
| Control Arm | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Knight, MD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Froedtert Hospital and the Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32027744 | Result | 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 trial. Blood Adv. 2020 Feb 11;4(3):467-476. doi: 10.1182/bloodadvances.2019000765. | |
| 29793446 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Propranolol |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Propranolol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Error | Unitless | Baseline (Pre-Transplant); 4 weeks post-transplant |
|
100 Days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Propranolol |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Edema of limb | General disorders | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Knight | Medical College of Wisconsin | 866-680-0505 | jknight@mcw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2016 | Feb 19, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 14, 2016 | Feb 19, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| C477592 | propranolol CR |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| 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. | 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. | 4 weeks after transplant |
| 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 |
| 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 |
| 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 |
| Knight JM, Kerswill SA, Hari P, Cole SW, Logan BR, D'Souza A, Shah NN, Horowitz MM, Stolley MR, Sloan EK, Giles KE, Costanzo ES, Hamadani M, Chhabra S, Dhakal B, Rizzo JD. Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation. BMC Cancer. 2018 May 24;18(1):593. doi: 10.1186/s12885-018-4509-0. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. |
|
|
|
| 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. | One propranolol subject was discontinued due to symptomatic hypotension. Two control subjects were discontinued doe to initiation of beta-blocker therapy for cardiac arrhythmia. | Posted | Mean | Standard Deviation | units on a scale | 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. | Posted | Count of Participants | Participants | No | 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. | Posted | Mean | Standard Deviation | Days | 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. | Posted | Mean | Standard Deviation | Days | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 100 days after transplant |
|
|
|
| 0 |
| 12 |
| 2 |
| 12 |
| 12 |
| 12 |
| EG001 | 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. | 0 | 13 | 3 | 13 | 13 | 13 |
| Fever | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Periorbital infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| 4-Week Anxiety Score |
|
|
| Very Good Partial Response |
|
| Complete Response |
|