Propranolol Dose Escalation in Lymphedema in Patients
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|ClinicalTrials.gov Identifier: NCT02595996|
Recruitment Status : Recruiting
First Posted : November 4, 2015
Last Update Posted : July 21, 2017
|Condition or disease||Intervention/treatment||Phase|
|Primary Lymphedema||Drug: Propranolol||Phase 2|
Lymphatic malformations (LMs) arise from abnormal development of lymphatic vasculature. Primary lymphedema is considered a form of LM. Recently, results in the investigators' laboratory demonstrated that propranolol, a pan beta-adrenergic receptor (βAR) antagonist, had cytotoxic and anti-proliferative effects against cells isolated from LM tissues. Preliminary results from treating symptomatic LM patients with propranolol at a dose range from 0.7-1mg/kg/day demonstrated a 70% positive response rate, with patients reporting improvement in their symptoms.
Propranolol has been used for different indications for many years. Propranolol is accepted for use in infants with hemangiomas and supraventricular tachycardia. Hemangeol was approved by the FDA for use in infants with hemangiomas. However, βAR antagonists are not without potential adverse effects, including hypotension, bradycardia, hypoglycemia, bronchospasms, and sleep disturbances. FDA-approved dose range for treating hemangiomas in infants (>5 weeks old, >2kg) ranged from 1-3mg/kg/day in divided doses. Propranolol doses of up to 4mg/kg/day has been used for pediatric supraventricular tachycardia. Therefore, the investigator's experience with propranolol use in LM patients have been at the low end of most accepted clinical indications. The investigators propose to escalate propranolol dosages up to 3mg/kg/day in this study, well below the dose ranges currently used in clinical settings.
This dose range of 0.7-1mg/kg/day was chosen for LM patients as it was the low end of dose range for infants treated with propranolol for problematic hemangiomas, a related vascular anomaly. At this dose, no significant hemodynamic adverse effects were noted in LM patients. However, when patients stopped propranolol or their dose fell below 0.7mg/kg/day, they suffered rebound worsening of their symptoms. Moreover, inflammatory events such as infections temporarily overcame the effects of 0.7-1mg/kg/day of propranolol. Thus, it is unknown whether maximum propranolol efficacy was achieved at the current dose range. The investigators propose to examine whether optimized propranolol usage for treatment of LM patients has been achieved. The primary endpoint for this study is to ascertain whether LM patients can tolerate higher doses of propranolol, as measured by known propranolol adverse effects and patient-reported symptoms. A secondary endpoint will address whether patient-reported LM symptoms and quality of life are improved with higher doses of propranolol; objective findings such as LM size on physical examination and imaging studies will be analyzed as well. In addition, LM tissue biopsies will acquired from patients before and after propranolol treatment for further analyses of disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema|
|Actual Study Start Date :||June 7, 2017|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Patients will be given propranolol in escalating doses
escalating doses of propranolol from 1mg/kg/day to 2mg/kg/day to 3mg/kg/day
Other Name: Inderal
- Number of patients that tolerated propranolol [ Time Frame: 8 weeks ]To assess whether patients tolerated propranolol
- Number of patients with improved quality of life based on self-reported questionnaires [ Time Frame: 8 weeks ]To assess subjective lymphedema symptoms improvements only - whether patients' general quality of life symptoms improved on propranolol treatment by self-reported questionnaires (SF 36)
- Number of patients with decreased fluid retention by weight [ Time Frame: 8 weeks ]To assess whether patients' lymphedema signs are improved on propranolol by weight (BMI kg/m^2) - objective signs of improvement of their lymphedema
- Number of patients with lower limb discrepancy [ Time Frame: 8 weeks ]To assess whether patients' lymphedema signs are improved on propranolol by limb girth discrepancy measurement (%) - objective signs of improvement of their lymphedema
- Number of patients with decreased fluid retention on MRI [ Time Frame: baseline to 8 weeks ]To assess whether patients' lymphedema signs are improved on propranolol - the decrease in fluid retention will be calculated by the measurement of fat (a number) divide by the measurement of fluid (a number) to yield a ratio - if a patient has a lower ratio at 8 weeks than at baseline, they will be reported in this catergory.
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): NCT02595996
|Contact: June K. Wu, MDemail@example.com|
|Contact: Roman Nowygrod, MDfirstname.lastname@example.org|
|United States, New York|
|New York, New York, United States, 10032|
|Contact: June Wu, MD email@example.com|
|Principal Investigator: June Wu, MD|
|Principal Investigator:||June K. Wu, MD||Columbia University|