Clinical Trial: Propranolol Dose Escalation in Lymphedema in Patients

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema

Brief Summary: This is a study to investigate the safety and efficacy of propranolol in the treatment of patients with primary lymphedema. The primary goal is to assess patient tolerability of increasing doses of propranolol. The secondary goal is to assess lymphedema symptoms and signs in response to propranolol treatment.

Detailed Summary:

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 re
Sponsor: Columbia University

Current Primary Outcome: Number of patients that tolerated propranolol [ Time Frame: 8 weeks ]

To assess whether patients tolerated propranolol


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Columbia University

Dates:
Date Received: September 18, 2015
Date Started: December 2015
Date Completion: December 2017
Last Updated: November 2, 2015
Last Verified: November 2015