Not listed
INTRATHECAL BACLOFEN AND PEDIATRIC DYSTONIA. - OVER 11,000 INFANTS ARE DIAGNOSED ANNUALLY WITH CEREBRAL PALSY (CP) WITH LIFETIME MEDICAL COSTS >$1.4 MILLION/PERSON. ELEVATED MUSCLE TONE INCLUDES DYSTONIA (INVOLUNTARY MUSCULAR CONTRACTION) AND SPASTICITY (VELOCITY-DEPENDENT MUSCLE STIFFNESS), WHICH OFTEN CO-EXIST, GREATLY IMPAIRING FUNCTION, MOBILITY, AND QUALITY OF LIFE AND CAUSING PAIN AND BONY DEFORMITIES. AFTER DECADES OF RESEARCH, DYSTONIA REMAINS POORLY UNDERSTOOD AND MANAGED. INTRATHECAL BACLOFEN (ITB) DELIVERED CONTINUOUSLY VIA AN IMPLANTED PUMP IS WIDELY USED TO MANAGE DYSTONIC CP DESPITE EQUIVOCAL EFFICACY DATA AND VERY LOW EVIDENCE SUPPORTING ITB USE. CO-MORBID SPASTICITY IS A MAJOR CONFOUNDER THAT CAN MASK DYSTONIA; FURTHER, MULTIPLE PATTERNS OF BRAIN MALFORMATION/INJURY CAUSE DYSTONIA AND MOST STUDIES FAIL TO ADDRESS DYSTONIA TRIGGERS, E.G., PAIN. A 2023 STUDY, HOWEVER, FOUND THAT DESPITE LIMITED DYSTONIA REDUCTION, ITB IMPROVED CAREGIVING EASE, PAIN, COMFORT, AND MOBILITY. THIS REVISED PROPOSAL SPECIFICALLY SEEKS TO OVERCOME THESE IDENTIFIED SERIOUS LIMITATIONS OF PRIOR STUDIES AND THOROUGHLY INVESTIGATE ITB'S EFFECTS USING AN ADEQUATELY POWERED, PROSPECTIVE OBSERVATIONAL COHORT DESIGN. THIS CLINICAL TRIAL WILL USE A STANDARDIZED TITRATION PROTOCOL TO OPTIMIZE ITB DOSING. WE HYPOTHESIZE THAT CHILDREN WITH MORE SEVERE BASELINE DYSTONIA, SPASTICITY, AND PAIN, AS WELL AS THOSE WITH WHITE MATTER BRAIN INJURY PATTERNS, WILL SHOW THE BEST OVERALL RESPONSE TO ITB. AIM 1) DETERMINE THE 12-MONTH EFFECTS OF ITB ON A COHORT OF 65 CLINICALLY REPRESENTATIVE, ITB NAÏVE, CHILDREN WITH DYSTONIC CP USING A STANDARDIZED TITRATION PROTOCOL AND A BATTERY OF ASSESSMENTS TO CAPTURE CRITICAL COMPONENTS OF THE CHILD'S FUNCTION AND WELL-BEING. AIM 2) COMPLETE A DETAILED CHARACTERIZATION OF BRAIN MALFORMATION AND INJURY PATTERNS IN CHILDREN WITH DYSTONIC CP. THIS WILL BE THE FIRST STUDY TO COMBINE MULTIPLE IMAGING ANALYSIS TECHNIQUES IN THIS POPULATION, INCLUDING THE MRI CLASSIFICATION SCALE FOR CP, LESION NETWORK MAPPING, AND TRACT BASED SPATIAL STATISTICS. AIM 3) EXPLORE POTENTIAL DIFFERENCES IN OUTCOME PATTERNS AS RELATED TO PATIENT CHARACTERISTICS AND USE FINDINGS TO GUIDE THE DEVELOPMENT OF A HIGHLY SENSITIVE MULTIDIMENSIONAL OR COMPOSITE MEASURE THAT CAPTURES CLINICALLY IMPORTANT AREAS OF CHANGE FOR THE CHILD AND FAMILY. THIS REVISED STUDY BUILDS ON NEW PRELIMINARY DATA AND CAPITALIZES ON THE EXPERTISE OF AN ESTABLISHED TRANSDISCIPLINARY TEAM, A HIGH-RESOURCE ACADEMIC CLINICAL ENVIRONMENT, AND A DIVERSE PARENT-PATIENT COUNCIL. THE STUDY'S FINDINGS ARE LIKELY TO HAVE HIGH IMPACT TO IMPROVE FUTURE TREATMENT OF CHILDREN WITH DYSTONIC CP, INCLUDING IDENTIFYING KEY PATIENT CHARACTERISTICS ASSOCIATED WITH MORE OR LESS POSITIVE OUTCOMES AND DEVELOPING A SENSITIVE, EFFICIENT MULTIDIMENSIONAL COMPOSITE MEASURE TO ASSESS TREATMENT RESPONSIVENESS.
$0 9/17/24 Not listed
INTRATHECAL BACLOFEN AND PEDIATRIC DYSTONIA. - OVER 11,000 INFANTS ARE DIAGNOSED ANNUALLY WITH CEREBRAL PALSY (CP) WITH LIFETIME MEDICAL COSTS >$1.4 MILLION/PERSON. ELEVATED MUSCLE TONE INCLUDES DYSTONIA (INVOLUNTARY MUSCULAR CONTRACTION) AND SPASTICITY (VELOCITY-DEPENDENT MUSCLE STIFFNESS), WHICH OFTEN CO-EXIST, GREATLY IMPAIRING FUNCTION, MOBILITY, AND QUALITY OF LIFE AND CAUSING PAIN AND BONY DEFORMITIES. AFTER DECADES OF RESEARCH, DYSTONIA REMAINS POORLY UNDERSTOOD AND MANAGED. INTRATHECAL BACLOFEN (ITB) DELIVERED CONTINUOUSLY VIA AN IMPLANTED PUMP IS WIDELY USED TO MANAGE DYSTONIC CP DESPITE EQUIVOCAL EFFICACY DATA AND VERY LOW EVIDENCE SUPPORTING ITB USE. CO-MORBID SPASTICITY IS A MAJOR CONFOUNDER THAT CAN MASK DYSTONIA; FURTHER, MULTIPLE PATTERNS OF BRAIN MALFORMATION/INJURY CAUSE DYSTONIA AND MOST STUDIES FAIL TO ADDRESS DYSTONIA TRIGGERS, E.G., PAIN. A 2023 STUDY, HOWEVER, FOUND THAT DESPITE LIMITED DYSTONIA REDUCTION, ITB IMPROVED CAREGIVING EASE, PAIN, COMFORT, AND MOBILITY. THIS REVISED PROPOSAL SPECIFICALLY SEEKS TO OVERCOME THESE IDENTIFIED SERIOUS LIMITATIONS OF PRIOR STUDIES AND THOROUGHLY INVESTIGATE ITB'S EFFECTS USING AN ADEQUATELY POWERED, PROSPECTIVE OBSERVATIONAL COHORT DESIGN. THIS CLINICAL TRIAL WILL USE A STANDARDIZED TITRATION PROTOCOL TO OPTIMIZE ITB DOSING. WE HYPOTHESIZE THAT CHILDREN WITH MORE SEVERE BASELINE DYSTONIA, SPASTICITY, AND PAIN, AS WELL AS THOSE WITH WHITE MATTER BRAIN INJURY PATTERNS, WILL SHOW THE BEST OVERALL RESPONSE TO ITB. AIM 1) DETERMINE THE 12-MONTH EFFECTS OF ITB ON A COHORT OF 65 CLINICALLY REPRESENTATIVE, ITB NAÏVE, CHILDREN WITH DYSTONIC CP USING A STANDARDIZED TITRATION PROTOCOL AND A BATTERY OF ASSESSMENTS TO CAPTURE CRITICAL COMPONENTS OF THE CHILD'S FUNCTION AND WELL-BEING. AIM 2) COMPLETE A DETAILED CHARACTERIZATION OF BRAIN MALFORMATION AND INJURY PATTERNS IN CHILDREN WITH DYSTONIC CP. THIS WILL BE THE FIRST STUDY TO COMBINE MULTIPLE IMAGING ANALYSIS TECHNIQUES IN THIS POPULATION, INCLUDING THE MRI CLASSIFICATION SCALE FOR CP, LESION NETWORK MAPPING, AND TRACT BASED SPATIAL STATISTICS. AIM 3) EXPLORE POTENTIAL DIFFERENCES IN OUTCOME PATTERNS AS RELATED TO PATIENT CHARACTERISTICS AND USE FINDINGS TO GUIDE THE DEVELOPMENT OF A HIGHLY SENSITIVE MULTIDIMENSIONAL OR COMPOSITE MEASURE THAT CAPTURES CLINICALLY IMPORTANT AREAS OF CHANGE FOR THE CHILD AND FAMILY. THIS REVISED STUDY BUILDS ON NEW PRELIMINARY DATA AND CAPITALIZES ON THE EXPERTISE OF AN ESTABLISHED TRANSDISCIPLINARY TEAM, A HIGH-RESOURCE ACADEMIC CLINICAL ENVIRONMENT, AND A DIVERSE PARENT-PATIENT COUNCIL. THE STUDY'S FINDINGS ARE LIKELY TO HAVE HIGH IMPACT TO IMPROVE FUTURE TREATMENT OF CHILDREN WITH DYSTONIC CP, INCLUDING IDENTIFYING KEY PATIENT CHARACTERISTICS ASSOCIATED WITH MORE OR LESS POSITIVE OUTCOMES AND DEVELOPING A SENSITIVE, EFFICIENT MULTIDIMENSIONAL COMPOSITE MEASURE TO ASSESS TREATMENT RESPONSIVENESS.
$680.9k 8/16/24