Nadolol for Proliferating Infantile Hemangiomas

Sponsor

The Hospital for Sick Children (Other)

Overall Status

Completed

CT.gov ID

NCT01010308

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to explore the efficacy and safety of Nadolol in hemangiomas of infancy.

The secondary objective is to assess the feasibility of conducting a randomized controlled trial comparing nadolol with corticosteroids and propranolol.

Condition or Disease	Intervention/Treatment	Phase
Infantile Hemangioma	Drug: Nadolol	Phase 2

Detailed Description

Systemic corticosteroids are currently the most frequent used medication for treatment of problematic infantile hemangiomas (IH's). Since June 2008, systemic propranolol has been an important addition to the therapeutic options for problematic IH, allowing decreased dependence on the systemic corticosteroids. So far, we have found excellent response with propranolol with minimal short-term side effects. Studies, which compared nadolol and propranolol in children with other conditions, suggest that nadolol is safer and more efficacious than propranolol. In addition, it has better dosing schedules and less central nervous system (CNS) penetration, making it suitable even for patients with suspected or proven PHACES syndrome.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Nadolol for Proliferating Infantile Hemangiomas: A Prospective Open Label Study With a Historical Control

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Group: The patients in this study are infants aged 1 month to 1 year of age with head and neck hemangiomas currently causing /or with impending function loss (e.g. vision, airway obstruction, feeding, etc), or hemangiomas currently causing/or with potential for facial disfigurement Infants aged 1 month to 1 year of age with head and neck hemangiomas that received treatment with systemic propranolol in the past 2 years as a control group	Drug: Nadolol Nadolol will be administered orally at home starting at 0.5 mg/kg/day divided into 2 doses. Weekly, if BP and heart rate are acceptable, the dose will be increased by 0.5 mg/kg/day up to 2 mg/kg/day.
No Intervention: Historical control group Ten infants (1-12 months of age) treated with propranolol will be identified from a Dermatology Database. Patients will be considered as controls if they were treated with propranolol before 1 year of age and had digital photography documentation of their hemangioma.
No Intervention: Angiogenesis marker control group The angiogenesis marker control group will consist of 6 -10 patients seen in the Dermatology clinic for conditions other than IH and not receiving corticosteroids or beta blockers.

Arm

Intervention/Treatment

Experimental: Intervention Group:

The patients in this study are infants aged 1 month to 1 year of age with head and neck hemangiomas currently causing /or with impending function loss (e.g. vision, airway obstruction, feeding, etc), or hemangiomas currently causing/or with potential for facial disfigurement Infants aged 1 month to 1 year of age with head and neck hemangiomas that received treatment with systemic propranolol in the past 2 years as a control group

Drug: Nadolol

Nadolol will be administered orally at home starting at 0.5 mg/kg/day divided into 2 doses. Weekly, if BP and heart rate are acceptable, the dose will be increased by 0.5 mg/kg/day up to 2 mg/kg/day.

No Intervention: Historical control group

Ten infants (1-12 months of age) treated with propranolol will be identified from a Dermatology Database. Patients will be considered as controls if they were treated with propranolol before 1 year of age and had digital photography documentation of their hemangioma.

No Intervention: Angiogenesis marker control group

The angiogenesis marker control group will consist of 6 -10 patients seen in the Dermatology clinic for conditions other than IH and not receiving corticosteroids or beta blockers.

Outcome Measures

Primary Outcome Measures

Proportion of subjects with at least 75% improvement in the extent of the hemangioma [Baseline, 6months]

Secondary Outcome Measures

The proportion of subjects with at least 50% improvement in the extent of the hemangiomas [Baseline and 6 months]
The proportion of subjects with at least 50% improvement in the extent of the hemangiomas
The percentage of patients with >75% improvement in the Nadolol group compared to a historical cohort of patients receiving propranolol. [6 months]
The percentage of patients with >75% improvement in the Nadolol group compared to a historical cohort of patients receiving propranolol.
The correlation between the changes in the levels of angiogenesis markers and clinical response to treatment. [6 months]
The correlation between the changes in the levels of angiogenesis markers and clinical response to treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Intervention Group

Infants aged 1 month to 1 year of age with head and neck hemangiomas currently causing /or with impending function loss (e.g. vision, airway obstruction, feeding, etc), or hemangiomas currently causing/or with potential for facial disfigurement.

Historical Control Group

Infants aged 1 month to 1 year of age with head and neck hemangiomas that received treatment with systemic propranolol in the past 2 years

Angiogenesis Marker Control Group

Infants aged 1 month to 1 year attending dermatology clinic

Exclusion Criteria:

Intervention Group

Patients with PHACES syndrome (proven) or suspected PHACES (plaque like hemangioma awaiting imaging).
Children with history of hypersensitivity to beta blockers
Children with personal history or family history of a first degree relative with asthma
Children with known renal impairment
Children with known cardiac conditions which may predispose to heart blocks
Personal history of hypoglycemia
Children on medications that may interact with beta blockers