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The primary endpoints were as follows: Anxiety Depression and Mood Scale (\n                      <jats:styled-content style=\"fixed-case\">ADAMS<\/jats:styled-content>\n                      ) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (\n                      <jats:styled-content style=\"fixed-case\">RSBQ<\/jats:styled-content>\n                      ) Fear\/Anxiety subscale, Parent Target Symptom Visual Analog Scale (\n                      <jats:styled-content style=\"fixed-case\">PTSVAS<\/jats:styled-content>\n                      ) top three concerns, Clinical Global Impression (\n                      <jats:styled-content style=\"fixed-case\">CGI<\/jats:styled-content>\n                      ), Parent Global Impression (\n                      <jats:styled-content style=\"fixed-case\">PGI<\/jats:styled-content>\n                      ), and the Kerr severity scale. Cardiorespiratory\u2010 and electroencephalography (\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      )\u2010based biomarkers were also analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were no significant differences between randomization groups. The majority of\n                      <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                      s were mild to moderate, although 12 episodes of serious\n                      <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                      s occurred. The Kerr severity scale,\n                      <jats:styled-content style=\"fixed-case\">ADAMS<\/jats:styled-content>\n                      Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      ) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      As in the phase 1 trial, rh\n                      <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\n                      \u20101 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.533","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T09:39:10Z","timestamp":1517391550000},"page":"323-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Placebo\u2010controlled crossover assessment of mecasermin for the 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