Primary LymphedemaPhase 2NCT02595996
Propranolol Dose Escalation in Lymphedema in Patients
A Phase 2 study testing Propranolol in people with Primary Lymphedema, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Primary Lymphedema
- What is being tested?
- Propranolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jun 2017to 8 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Primary lymphedema
- Measurable disease
- Adequate functional status: Karnofsky >50% (>age 16), Lanky >50 (<age 16),
- No prior therapy within 4 weeks of enrollment
- Adequate bone marrow, renal function, cardiac, and pulmonary function, negative pregnancy test (for women).
Who cannot join
- Secondary lymphedema
- Patients already receiving other investigational drugs
- Patients with known contraindications to receiving propranolol
- Other medical comorbidities including but not limited to: pheochromocytoma, bradycardia, bronchospasm/reactive airway disease, decompensated heart failure, heart block, ongoing active infections.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema
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.
Read the detailed description
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.
- Conditions
- Primary Lymphedema
- Being tested
- Propranolol
- Medical subject headings
- Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Also called Inderal
escalating doses of propranolol from 1mg/kg/day to 2mg/kg/day to 3mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients will be given propranolol in escalating doses Receives: Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients That Tolerated Propranolol
To assess whether patients tolerated propranolol
Measured: 8 weeks
Secondary outcomes (4)
Number of Patients With Improved Quality of Life Based on Self-reported Questionnaires
To assess subjective lymphedema symptoms improvements only - whether patients' general quality of life symptoms improved on propranolol treatment by self-reported questionnaires (SF 36)
Measured: 8 weeks
Number of Patients With Decreased Fluid Retention by Weight
To assess whether patients' lymphedema signs are improved on propranolol by weight (BMI kg/m^2) - objective signs of improvement of their lymphedema
Measured: 8 weeks
Number of Patients With Lower Limb Discrepancy
To assess whether patients' lymphedema signs are improved on propranolol by limb girth discrepancy measurement (%) - objective signs of improvement of their lymphedema
Measured: 8 weeks
Number of Patients With Decreased Fluid Retention on MRI
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 category.
Measured: baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study start7 Jun 2017
- Primary completion8 Oct 2020
- Study completion8 Oct 2020
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary LymphedemaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, June Wu, Columbia University
- Investigators
- June K. Wu, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595996
- Sponsor's protocol ID
- AAAP9262
- Status last verified
- Sep 2021
- First submitted
- 18 Sep 2015
- Last updated
- 22 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema
- ClinicalTrials.gov ID
- NCT02595996
- Acronym / sponsor ID
- AAAP9262
- Conditions
- Primary Lymphedema
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 7 Jun 2017 (actual)
- Primary completion
- 8 Oct 2020 (actual)
- Study completion
- 8 Oct 2020 (actual)
- First posted
- 4 Nov 2015 (estimated)
- Results
- Posted 22 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: PropranololPatients will be given propranolol in escalating doses |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Primary lymphedema
- Measurable disease
- Adequate functional status: Karnofsky >50% (>age 16), Lanky >50 (<age 16),
- No prior therapy within 4 weeks of enrollment
- Adequate bone marrow, renal function, cardiac, and pulmonary function, negative pregnancy test (for women).
Key exclusion criteria (4 listed)
- Secondary lymphedema
- Patients already receiving other investigational drugs
- Patients with known contraindications to receiving propranolol
- Other medical comorbidities including but not limited to: pheochromocytoma, bradycardia, bronchospasm/reactive airway disease, decompensated heart failure, heart block, ongoing active infections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropranololAlso: Inderalescalating doses of propranolol from 1mg/kg/day to 2mg/kg/day to 3mg/kg/day | Drug | Treatment |
Primary outcome
Number of Patients That Tolerated Propranolol
Time frame: 8 weeks
To assess whether patients tolerated propranolol
4 secondary outcomes
Number of Patients With Improved Quality of Life Based on Self-reported Questionnaires
Time frame: 8 weeks
Number of Patients With Decreased Fluid Retention by Weight
Time frame: 8 weeks
Number of Patients With Lower Limb Discrepancy
Time frame: 8 weeks
Number of Patients With Decreased Fluid Retention on MRI
Time frame: baseline to 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
June K. Wu, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Propranolol in people with Primary Lymphedema, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients That Tolerated Propranolol (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2021.