Open AccessPlacebo‐controlled crossover assessment of mecasermin for the treatment of Rett syndrome
Author(s) -
O'Leary Heather M.,
Kaufmann Walter E.,
Barnes Katherine V.,
Rakesh Kshitiz,
Kapur Kush,
Tarquinio Daniel C.,
Cantwell Nicole G.,
Roche Katherine J.,
Rose Suzanne A.,
Walco Alexandra C.,
Bruck Natalie M.,
Bazin Grace A.,
Holm Ingrid A.,
Alexander Mark E.,
Swanson Lindsay C.,
Baczewski Lauren M.,
Mayor Torres Juan M.,
Nelson Charles A.,
Sahin Mustafa
Publication year - 2018
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.533
Subject(s) - medicine , clinical global impression , rett syndrome , placebo , crossover study , anxiety , mood , population , randomization , visual analogue scale , pediatrics , hyperventilation , electroencephalography , physical therapy , clinical trial , psychiatry , biochemistry , chemistry , alternative medicine , environmental health , pathology , gene
Abstract Objective To measure the efficacy of mecasermin (recombinant human insulin‐like growth factor 1, rh IGF ‐1), for treating symptoms of Rett syndrome ( RTT ) in a pediatric population using a double‐blind crossover study design. Methods Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rh IGF ‐1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28‐week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale ( ADAMS ) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire ( RSBQ ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale ( PTSVAS ) top three concerns, Clinical Global Impression ( CGI ), Parent Global Impression ( PGI ), and the Kerr severity scale. Cardiorespiratory‐ and electroencephalography ( EEG )‐based biomarkers were also analyzed. Results There were no significant differences between randomization groups. The majority of AE s were mild to moderate, although 12 episodes of serious AE s occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography ( EEG ) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation As in the phase 1 trial, rh IGF ‐1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.