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Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience.

ABSTRACT: BACKGROUND:This study aimed to describe recruitment challenges encountered during a phase IIa study of vixotrigine, a state and use-dependent Nav1.7 channel blocker, in individuals with trigeminal neuralgia. METHODS:This was an international, multicenter, placebo-controlled, randomized withdrawal study that included a 7-day run-in period, a 21-day open-label phase, and a 28-day double-blind phase in which patients (planned n =?30) were randomized to vixotrigine or placebo. Before recruitment, all antiepileptic drugs had to be stopped, except for gabapentin or pregabalin. After the trial, patients returned to their original medications. Patient recruitment was expanded beyond the original five planned (core) centers in order to meet target enrollment (total recruiting sites N =?25). Core sites contributed data related to patient identification for study participation (prescreening data). Data related to screening failures and study withdrawal were also analyzed using descriptive statistics. RESULTS:Approximately half (322/636; 50.6%) of the patients who were prescreened at core sites were considered eligible for the study and 56/322 (17.4%) were screened. Of those considered eligible, 26/322 (8.1%) enrolled in the study and 6/322 (1.9%) completed the study. In total, 125 patients were screened across all study sites and 67/125 (53.6%) were enrolled. At prescreening, reasons for noneligibility varied by site and were most commonly diagnosis change (78/314; 24.8%), age?>?80?years (75/314; 23.9%), language/distance/mobility (61/314; 19.4%), and noncardiac medical problems (53/314; 16.9%). At screening, frequently cited reasons for noneligibility included failure based on electrocardiogram, insufficient pain, and diagnosis change. CONCLUSIONS:Factors contributing to recruitment challenges encountered in this study included diagnosis changes, anxiety over treatment changes, and issues relating to distance, language, and mobility. Wherever possible, future studies should be designed to address these challenges. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01540630 . EudraCT, 2010-023963-16. 07 Aug 2015.

SUBMITTER: Zakrzewska JM

PROVIDER: S-EPMC6307274 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience.

Zakrzewska Joanna M JM Palmer Joanne J Bendtsen Lars L Di Stefano Giulia G Ettlin Dominik A DA Maarbjerg Stine S Obermann Mark M Morisset Valerie V Steiner Deb D Tate Simon S Cruccu Giorgio G

Trials 20181227 1

<h4>Background</h4>This study aimed to describe recruitment challenges encountered during a phase IIa study of vixotrigine, a state and use-dependent Nav1.7 channel blocker, in individuals with trigeminal neuralgia.<h4>Methods</h4>This was an international, multicenter, placebo-controlled, randomized withdrawal study that included a 7-day run-in period, a 21-day open-label phase, and a 28-day double-blind phase in which patients (planned n = 30) were randomized to vixotrigine or placebo. Before ...[more]

PMID: 30587219

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Project description:Background: Trigeminal neuralgia (TN) is a recognized pain condition the treatment of which can be very challenging. Various surgical interventions can be applied in cases of therapy-resistance to drug treatments. The central lateral thalamotomy (CLT) against neurogenic (or neuropathic) pain is based on multiarchitectonic histological as well as physiopathological studies, and integrates the nucleus in a large thalamocortical (TC) and corticocortical network responsible for the sensory, cognitive and affective/emotional components of pain. The advent of the magnetic resonance imaging guided high intensity focused ultrasound (MRgFUS) brought a strong reduction in morbidity and increase in accuracy compared to penetration techniques. Objective: This study was aimed at analyzing the outcome of bilateral MRgFUS CLT for chronic therapy-resistant trigeminal pain, all performed in one single center. Methods: Patients were categorized in Classical, Idiopathic and Secondary TN. By definition, paroxysms lasted for seconds up to 2 min. All patients were screened for trigeminal neurovascular conflict. In case of classical TN, microvascular decompression was proposed. Therapy-resistance and thus indication for MRgFUS CLT was based on the lack of efficacy and/or side effects of antiepileptic and antidepressant drugs. Good outcome was defined by a pain relief ?50%. Results: Eight patients suffering from chronic therapy-resistant trigeminal neuralgia were treated. All suffered from pain with paroxysmal character. Six patients reported additionally continuous pain. Mean follow-up was 53 months (range: 12-92, median: 60 months). The mean pain relief assessed by patients was 51% (median: 58%, range: 0-90%) at 3 months, 71% (median: 65%, range: 40-100%) at 1 year and 78% (median: 75%, range: 50-100%) at their longest follow-up. This represents 63% good outcomes at 3 months, 88% at 1 year and 100% at last follow-up. Frequency of the mean pain paroxysms decreased from 84 per day preoperative to 3.9 at 1 year postoperatively. There were no serious adverse events in this series. Conclusion: Our study provides preliminary support for the safety and efficacy of MRgFUS CLT, a histologically and pathophysiologically based medial thalamotomy against chronic therapy-resistant trigeminal neuralgia.

Project description:BackgroundTrigeminal neuralgia (TN) is considered one of the most painful illnesses known to medical practice. Little is known about TN in Ethiopia. Our study aimed to assess clinical characteristics, treatment, and associated factors of TN.MethodA cross-sectional study was conducted on a total of 61 patients with confirmed Trigeminal neuralgia visiting outpatient neurology clinics of two government teaching Hospitals and two private health facilities in Addis Ababa, Ethiopia between June 2019 and March 2020.ResultsOur participants' age range between 21 and 78 years with mean ± SD age of 50.7 ± 14.2 years. Males accounted for 50.8%. Twenty-five (41%) reported a prior history of one or more tooth extraction on the painful side. In the majority (68.9%) of the patient's right side of the face was affected. The mandibular nerve was the commonly involved branch (47.5%). Fifty-five (90.2%) of patients fulfilled criteria for classical TN and 9.8% had symptomatic TN. The majority of the participants reported mixed types of pain such as burning, lancinating, and electric shock-like. Well defined trigger zone was identified in one-third (36%) of cases. Carbamazepine was the most commonly prescribed drug with a median dose of 600 mg (IQR: 400 - 1000 mg). Two-third of the patients reported prominent satisfaction. The mean (± SD) dose of carbamazepine used to control the pain was significantly higher among those with dental extraction history as compared to those with no history of dental extraction (736 ± 478.6 mg Vs 661.1 ± 360.4 mg, respectively, T = - 2.06, p = 0.04 95% CI:-213.41 to - 2.98). A statistically significant number of patients who had single branch involvement reported prominent satisfaction with their treatment as compared to those who had more than one branch involvement. (95% CI: 1.3-3.8: p = 0.006).ConclusionThe majority of our patients had Classical TN in the mandibular nerve distribution on the right side of the face and well satisfied with carbamazepine only treatment. Furthermore, we observed a higher proportion of dental extraction among our patients, hinting at the scale of miss and delayed-diagnoses. Thus, we recommend conducting a well-designed prospective study to support our findings.

Project description:ObjectiveTo compare complete neuroendoscopic and microscopic microvascular decompression (MVD) in primary trigeminal neuralgia (PTN) and their impacts on the microstructure of the trigeminal nerve.MethodsEighty-seven PTN patients admitted in our hospital from July 2017 to December 2019 were selected for this prospective study and divided into the endoscopic group (n=45) (complete neuroendoscopic MVD) and the microscope group (n=42) (microscopic MVD) according to the treatment method each patient underwent. All the patients underwent MRI scanning, and the fractional anisotropy (FA) scores and the apparent diffusion coefficient (ADC) values of the neurovascular compression (NVC) sites were measured. The operation times, the treatment efficacy, the microstructural changes in the trigeminal nerve, the complications, and the recurrence and mortality rates at one year after the operations were compared.ResultsThe endoscopic group observed a superior therapeutic effect compared with the microscope group one year after the surgeries (P=0.046). After the surgeries, the endoscopic group observed a greater increase in their FA values and a larger decline in their ADC values than the microscope group did (P=0.014, 0.015, 0.011, 0.002). The complication rate in the endoscopic group was 11.11%, and the complication rate in the microscopic group was 30.95% (P=0.022). One year after the surgeries, we found a lower recurrence rate in the endoscopic group (P=0.001). The perforator vessels from the offending vessel to the outlet area of the durmedulla, the distances between the front edge of the bone window and the inner surfaces of the petrous part of the temporal bone ≥ the distance between the duration ≥ the duration of conventional MVD were independent risk factors for complications after MVD in the hemifacial spasm patients (P=0.001, 0.037, 0.023, 0.005).ConclusionComplete neuroendoscopic MV yields better long-term treatment outcomes than microscopic MVD, and it is more effective at improving the microstructure of the trigeminal nerve and has fewer postoperative complications.

Dataset Information

Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience.

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Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience.

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