A Systematic Review and Meta‑Analysis protocol of Neuromodulation therapies versus standard medical therapy (or sham) for patients with chronic or frequent episodic cluster headache
Supervisor Name
Zaher Nazzal
Supervisor Email
znazzal@najah.edu
University
An-Najah National University, faculty of Medicine and Health Sciences
Research field
Medical Sciences
Bio
Dr. Zaher Ahmad Nazzal is a Palestinian physician, academic, and researcher specializing in Community Medicine. Born on September 1, 1972, he earned his MD from Istanbul University’s Cerrahpaşa Medical Faculty in 1999 and completed his Arab Board certification in Community Medicine at Hamad Medical Corporation, Doha, Qatar, in 2009. With over two decades of experience, Dr. Nazzal has made substantial contributions to community health, medical education, and health systems research in Palestine and the broader Eastern Mediterranean region. Since 2011, Dr. Nazzal has served as an Associate Professor in the Department of Family and Community Medicine at An-Najah National University (ANNU). Over the years, he has held several key leadership roles, including Head of the Department of Family and Community Medicine, Head of the Research Unit, and Coordinator of Clinical Scientific Research at ANNU. He played an essential role in establishing the An-Najah Child Institute for Child Developmental Disorders and has participated impactful initiatives such as the HERA Project, which addresses healthcare responses to violence and abuse. Dr. Nazzal has taught research methods courses to medical and Master students for more than ten years, equipping generations of learners with essential skills in scientific inquiry and evidence-based practice. He has supervised over 150 research projects, many of which have contributed meaningfully to local and regional health knowledge. Dr. Nazzal’s research interests span a wide array of critical public health issues, including non-communicable diseases, antimicrobial resistance, maternal and child health, and pandemic response, particularly during the COVID-19 crisis. To date, he has published more than 100 articles in international peer-reviewed journals, significantly advancing understanding of health challenges in resource-limited and conflict-affected settings. He is an active member of several professional bodies, including the Palestinian Board Committee of Community Medicine and the Arab Board of Community Medicine. Fluent in Arabic, English, and Turkish, Dr. Nazzal is also proficient in statistical analysis software (e.g., SPSS) and reference management tools. ORCID Link/ID: https://orcid.org/0000-0002-2655-6109 SCOPUS ID: 36988148800 Google scholar ID: xjDQhMcAAAAJ ANNU Staff page: https://staff.najah.edu/en/profiles/3513
This project is a systematic review and network meta-analysis protocol designed to evaluate the efficacy and safety of neuromodulation therapies for patients with chronic or frequent episodic cluster headache (CH) who are poorly controlled by standard medications. • Rationale: Cluster headache is a severe and debilitating condition. A significant proportion of patients (up to one-third) do not respond adequately to standard medical therapy (e.g., oxygen, triptans, verapamil). While neuromodulation therapies like non-invasive vagus nerve stimulation (nVNS), sphenopalatine ganglion (SPG) stimulation, and occipital nerve stimulation (ONS) show promise, the existing evidence is varied. There is a lack of a comprehensive, recent meta-analysis that directly compares these interventions for this specific, treatment-resistant patient population, creating a knowledge gap for clinicians. • Objectives: The primary aim is to determine whether neuromodulation therapies are superior to standard medical therapy or a sham device in reducing attack frequency and severity, and increasing the proportion of patients who experience a ≥50% reduction in attacks (responder rate). Secondary objectives include comparing the effectiveness of the different neuromodulation therapies against each other and assessing their cost-effectiveness and safety. • Methodology: The study will adhere to rigorous systematic review standards (PRISMA guidelines) and be prospectively registered in PROSPERO. A comprehensive search of multiple electronic databases (e.g., PubMed, Embase, Cochrane Library) and grey literature will be conducted. Two reviewers will independently screen studies, extract data, and assess the risk of bias using standardized tools (Cochrane RoB-2, ROBINS-I). A network meta-analysis will be performed using R software to allow for direct and indirect comparisons of all interventions. • Significance: This study will synthesize the highest quality available evidence to provide clinicians with clear, data-driven guidance on the use of neuromodulation therapies for medically refractory cluster headache. The findings are expected to inform clinical decision-making and potentially influence future treatment guidelines.
