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.

Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study.

Objective: To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG).

Methods: The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible.

A cluster randomized trial to evaluate a centralized remote clinical pharmacy service in large, health system primary care clinics.

Background: We developed a remote cardiovascular risk service (CVRS) managed by clinical pharmacists to support primary care teams. The purpose of this study was to examine whether the CVRS could improve guideline adherence in primary care clinics with diverse geographic and patient characteristics.

Methods: This study was a cluster-randomized trial initiated in 20 primary care clinics across the US.

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.

Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis.

Background: Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data.

Objective: To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial.

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.

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.

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability.

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.

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.

Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen.

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke.

Objective: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients.

Motor Function Test Reliability During the NeuroNEXT Spinal Muscular Atrophy Infant Biomarker Study.

Background: The NeuroNEXT SMA Infant Biomarker Study, a two year, longitudinal, multi-center study of infants with SMA type 1 and healthy infants, presented a unique opportunity to assess multi-site rater reliability on three infant motor function tests (MFTs) commonly used to assess infants with SMA type 1.

Objective: To determine the effect of prospective MFT rater training and the effect of rater experience on inter-rater and intra-rater reliability for the Test of Infant Motor Performance Screening Items (TIMPSI), the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and the Alberta Infant Motor Scale (AIMS).

Methods: Training was conducted utilizing a novel set of motor function test (MFT) videos to optimize accurate MFT administration and reliability for the study duration.

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.

Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA!

Background/aims: Recruitment and retention of research participants are challenging and critical components of successful clinical trials and natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly challenging population to study due to their fragile and complex medical issues, poor prognosis and, until 2016, a lack of effective therapies. Recruitment of healthy infants into clinical trials and natural history studies is also challenging and sometimes assumed to not be feasible.

Natural history of infantile-onset spinal muscular atrophy.

Objective: Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes.

Methods: A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants and 27 control infants aged <6 months.

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.

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis.

Background: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown.

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.

Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study.

Objective: This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).

Methods: This prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network.

Consistency of quantitative scores of hypoglycemia severity and glycemic lability and comparison with continuous glucose monitoring system measures in long-standing type 1 diabetes.

Background: In long-standing type 1 diabetes (T1D), loss of endogenous insulin secretion and glucose dysregulation can lead to severe hypoglycemia and associated complications. Here, we report the serial consistency and the correlation between different scores that characterize glucose dysregulation using self-monitoring of blood glucose (SMBG), in a cohort of T1D individuals being evaluated for transplant eligibility in Clinical Islet Transplantation Consortium trials.

Subjects And Methods: In total, 152 C-peptide-negative T1D subjects with at least one severe hypoglycemia episode in the prior year documented SMBG at enrollment and every 6 months until deemed ineligible or transplanted.

Retirement and weight changes among men and women in the health and retirement study.

Objectives: Older adults may experience weight changes upon retirement for a number of reasons, such as being less physically active; having less structured meal times; and consuming food in response to losing personal identity, the potential for social interactions, or the sense of accomplishment derived from working. The purpose of this study was to determine whether retirement was associated with either weight gain or weight loss.

Methods: We used the 1994-2002 Health and Retirement Study to determine whether retirement between biennial interviews was associated with weight change, separately for men (n = 1,966) and women (n = 1,759).

Impact of functional limitations and medical comorbidity on subsequent weight changes and increased depressive symptoms in older adults.

Objective: The primary goal of this study was to determine the effect of the onset of major medical comorbidity and functional decline on subsequent weight change and increased depressive symptoms.

Methods: The sample included a prospective cohort of 53 to 63 year olds (n = 10,150) enrolled in the Health and Retirement Study. Separate lagged covariate models for men and women were used to study the impact of functional decline and medical comorbidity on subsequent increases in depressive symptoms and weight change 2 years later.

Weight and depressive symptoms in older adults: direction of influence?

Objective: . The purpose of this study was to clarify the direction of the relationship between changes in depressive symptoms and changes in weight in older adults. Methods.