Neurofibromatosis

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this period.

Researchers are evaluating two different educational letter interventions to improve the rate of recommended health screenings for people with Neurofibromatosis 1 (NF1) who do not usually attend specialized NF clinics. The study focuses on both adults with NF1 and parents or guardians of children with NF1 across the U.S. The goal is to find out which approach better supports patients during their annual wellness visits with primary care providers by promoting evidence-based care. Participants will be randomly assigned to receive one of two types of letters about NF1 care, one addressed to themselves and one to their primary care clinician. These letters provide information about NF1 care recommendations to be reviewed before the participant's upcoming annual wellness visit. After this visit, participants will complete a follow-up online survey, and a small group may take part in virtual interviews to share their experiences. The study is fully decentralized and does not require any visits to Massachusetts General Hospital. Participants will complete online surveys before and after their wellness visit to assess the impact of the interventions. The main outcome measured is whether participants received the recommended NF1 health screenings within two weeks after their primary care visit. Secondary measures include patient activation and satisfaction with care. Throughout the study, all interactions and data collection are done remotely, and participation continues until after the follow-up survey is completed.

Researchers are investigating the effects of a multidomain lifestyle intervention to slow cognitive decline and dementia risk in elderly residents aged 60 to 80 in Zhejiang Province, China. The study builds on findings from Finland, where a similar approach combining physical activity, nutrition, cognitive training, social activities, and vascular risk management showed promise in healthy older adults at risk of cognitive decline. This trial aims to explore how such an intervention may change brain structure and function as well as cognitive abilities in an Asian population. Participants are randomly assigned to either a structured multidomain intervention group or a self-guided control group. The intervention group receives tailored nutritional guidance, cognitive training, physical exercises, and vascular risk monitoring, all adapted to Chinese cultural norms. The control group receives regular health education campaigns and basic health monitoring every 6 to 12 months. This trial runs for two years with ongoing assessments to evaluate the impact of these lifestyle changes. During the study, participants undergo various evaluations including cognitive tests measuring global and domain-specific cognition, neuroimaging scans like MRI and fMRI, laboratory blood tests, and physical performance measures such as grip strength and gait speed. Questionnaires assess quality of life, depression, sleep quality, and daily activities. Researchers also monitor cardiovascular health, dementia onset, and falls. This comprehensive monitoring will help determine the intervention's effects on brain health and daily functioning over the 24-month period.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation (DBS) for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.

This research aims to evaluate postoperative respiratory complications (PORC) in children with obstructive sleep apnea (OSA) who undergo (adeno)tonsillectomy. It combines data from two centers: University Hospital Antwerp and Heim Pal National Pediatric Institute in Hungary. The study examines how common these complications are and whether they vary according to different health conditions such as obesity, craniofacial malformations, Down syndrome, or neurological disorders that affect airway muscle tone. Data come from a retrospective analysis of electronic health records originally collected in two prospective studies. These records include children who had (adeno)tonsillectomy for OSA, with postoperative care following a set protocol. The study looks at factors like the obstructive apnea-hypopnea index, oxygen levels during sleep studies, age at surgery, and presence of other health conditions to understand their relationship with PORC and to help develop a management plan. Participants' information was collected without needing additional consent because it uses existing anonymized data. Researchers assess the prevalence of PORC within 24 hours after surgery and analyze how different factors affect this risk. This study does not involve new treatments but reviews existing data to improve postoperative care. The study includes children aged 1 to 18 years who had (adeno)tonsillectomy for OSA, with follow-up limited to the immediate postoperative period.

Researchers are studying how muscle and brain interactions relate to neurodegenerative diseases (NDGs) such as Amyotrophic Lateral Sclerosis, Alzheimer's Disease, and Parkinson's Disease, as well as aging. The study explores whether changes at the neuromuscular junction, where muscle and nerve communicate, contribute to these conditions. It aims to identify factors that influence brain-muscle connections and how these may predict disease progression or aging outcomes. This observational case-control study includes two groups: a "Good Aging" group of adults aged 60 or older without muscle or neurological impairments, and a "Bad Aging" group with patients diagnosed with NDGs or severe acquired brain injury, some with sarcopenia or cognitive issues. Researchers will collect clinical and biological data, including biomarkers, microRNA, and extracellular vesicle analyses, to better understand the muscle-brain relationship and movement issues. Participants will undergo assessments including the Edmonton Frail Scale at the start and after six months to measure frailty changes. The study will gather neurological and muscular phenotyping data to track participants' health trajectories. The study spans from baseline to a 6-month follow-up, monitoring physical and cognitive function to inform future clinical strategies for minimizing risks linked to aging and neurological disorders.

Researchers are evaluating HLX-1502 in an open-label, single-arm phase 2 study focused on people aged 16 and older with Neurofibromatosis Type 1 (NF1) who have progressive or symptomatic plexiform neurofibromas (PN). The study also includes a smaller group of participants aged 12 to 15 to investigate safety and effects in this younger group. The goal is to assess how well participants tolerate HLX-1502 and how it affects their condition. Participants will take an oral dose of HLX-1502 three times daily, with or without food, in 28-day cycles. The initial treatment period includes 12 cycles. Those showing partial response, stable disease after prior progression, or clinical improvement may continue treatment for an additional 12 cycles, totaling 24 cycles. This approach aims to explore both short-term and extended treatment effects. During the study, participants will have measurable PNs evaluated by volumetric MRI to monitor tumor response. Researchers will assess the PN response rate at 12 and 24 months, safety, tolerability, pharmacokinetics, and duration and time to response. Participants will be monitored regularly for organ function, performance status, and overall health, with study visits and procedures conducted throughout the treatment period and follow-up. The total study duration varies according to treatment response and continuation criteria.

Researchers are studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.

Researchers are evaluating the safety and effectiveness of combining trametinib and azacitidine in children and young adults newly diagnosed with juvenile myelomonocytic leukemia (JMML). This study focuses on two groups: lower-risk patients and high-risk patients, defined by specific genetic and molecular features. The trial aims to determine how well these drug combinations work and their safety in treating JMML. Lower-risk patients will receive daily azacitidine for five days combined with daily trametinib for 28 days per treatment cycle, for up to twelve cycles. High-risk patients will receive a combination of azacitidine, fludarabine, and cytarabine for five days along with daily trametinib for 28 days per cycle, for up to two cycles. These treatments are given through oral and intravenous methods, depending on the drug, and are tailored to the patient's risk category. Participants will undergo evaluations to monitor safety and treatment effects during and after each treatment cycle. Assessments include blood tests, genetic studies, kidney, liver, and heart function checks, and monitoring for side effects. The study will measure safety outcomes at the end of the first treatment cycle plus 30 days. Patients are followed throughout treatment courses lasting up to twelve cycles for lower-risk or two cycles for high-risk JMML, with ongoing monitoring to ensure their well-being.

Researchers are investigating the safety and effectiveness of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS) using the NaviFUS System in patients with recurrent glioblastoma multiforme (rGBM). This pivotal, randomized, open-label study compares standard care BEV alone to BEV combined with FUS in patients who have previously undergone surgery, radiotherapy, and chemotherapy with temozolomide. BEV is considered the best current treatment choice for these patients after prior therapies. Participants will be randomly assigned to one of two groups. One group will receive BEV alone via intravenous infusion at a dose of 10 mg/kg over 30-90 minutes every two weeks. The other group will receive the same BEV treatment followed by administration of microbubbles (SonoVue®) at 0.1 mL/kg and focused ultrasound exposure controlled by the NaviFUS System. Treatments will continue every two weeks for up to 34 weeks or until disease progression, intolerable side effects, non-compliance, or withdrawal. During the study, participants will be monitored through regular assessments including MRI scans, quality of life questionnaires, cognitive tests (Mini-Mental State Examination), and evaluation of corticosteroid use and adverse events. The primary outcome is progression-free survival at six months. Secondary outcomes include survival rates up to two years, tumor response, local disease control, and performance status. The total study participation can last up to 36 months with ongoing safety and efficacy monitoring.