Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial.

Importance: Cryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence.

Effects of AFQ056 on language learning in fragile X syndrome.

BACKGROUNDFXLEARN, the first-ever large multisite trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of metabotropic glutamate receptor type 5 (mGluR5) negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3- to 6-year-old children with FXS, expected to have more learning plasticity than adults, for whom prior trials of mGluR5 NAMs have failed.METHODSAfter a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language-learning intervention was implemented for both groups.

Impact of preventive pill-based treatment on migraine days: A secondary outcome study of the Childhood and Adolescent Migraine Prevention (CHAMP) trial and a comparison of self-report to nosology-derived assessments.

Objective: To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days.

Multimodal Assessment of Medication Adherence Among Youth With Migraine: An Ancillary Study of the CHAMP Trial.

Objective: Examine preventive medication adherence among youth with migraine.

Methods: Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications.

Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial.

Objective: Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study.

Methods: Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo.

Prevalence of Headache Days and Disability 3 Years After Participation in the Childhood and Adolescent Migraine Prevention Medication Trial.

Importance: Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained.

Objective: To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period.

Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype.

Objective: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis.

Background: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown.

Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial.

Importance: There is a critical need for careful and independent validation of reported symptomatic efficacy and dopaminergic biomarker changes induced by nilotinib in Parkinson disease (PD).

Objectives: To assess safety and tolerability of nilotinib in participants with moderately advanced PD. Secondary and exploratory objectives were to assess its affect on PD disability, pharmacokinetics, cerebrospinal fluid (CSF) penetration, and biomarkers.

Effects of Ibudilast on MRI Measures in the Phase 2 SPRINT-MS Study.

Objective: To determine whether ibudilast has an effect on brain volume and new lesions in progressive forms of multiple sclerosis (MS).

Methods: A randomized, placebo-controlled, blinded study evaluated ibudilast at a dose of up to 100 mg over 96 weeks in primary and secondary progressive MS. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks.

Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis.

Background: The SPRINT-MS trial demonstrated benefit of ibudilast on brain atrophy over 96 weeks in progressive multiple sclerosis (MS). Optical coherence tomography (OCT) was performed in all trial participants.

Objective: Report the OCT results of the SPRINT-MS trial.

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis.

Background: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.

Methods: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks.

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine.

Background: Which medication, if any, to use to prevent the headache of pediatric migraine has not been established.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo.

The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report on Baseline Characteristics of Participants.

Objective: To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).

Methods: Children and adolescents (age 8-17 years old, inclusive) diagnosed with migraine with or without aura, having headaches at least four times per month were enrolled from 2012 through 2014. The trial involved a baseline period (minimum of 28 days) during which prospective diaries were completed and demographics and headache features obtained.