Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers. METHODS: A central coordination center was established to design and conduct the program. Templated documents and processes were developed to streamline study design, regulatory submissions, and clinical operations across protocols. The program included three protocols and provided access to IPs that were being tested in respective regimens of the HEALEY ALS Platform Trial (verdiperstat, CNM-Au8, and pridopidine). Clinical and safety data were collected in all EA protocols (EAPs). The program cohorts comprised participants who were not eligible for the platform trial, including participants at advanced stages of disease progression and with long disease duration. RESULTS: A total of 85 participants were screened across the 3 EAPs from July 2021 to September 2022. The screen failure rate was 3.5%. Enrollment for the regimens of the platform trial was completed as planned and results informed the duration of the corresponding EAP. The verdiperstat EAP was concluded in December 2022. Mean duration of participation in the verdiperstat EAP was 5.8 ± 4.1 months. The CNM-Au8 and pridopidine EAPs are ongoing. DISCUSSION: Multicenter EAPs conducted in parallel to randomized clinical trials for ALS can successfully enroll participants who do not qualify for clinical trials.

[Spontaneous internal carotid artery dissection with paralysis of lower cranial nerves: case report]. / Dissecção espontânea de artéria carótida interna com paralisia de nervos cranianos inferiores: relato de caso.

Spontaneous internal carotid artery dissection is a rare event that strikes patients at their productive age. As early intervention frequently determines a significant improvement, it is important to broaden the knowledge of the clinical, pathogenic and pathophysiological aspects of this disease. The objective is making an early diagnosis and treatment to avoid a bad outcome. We report the case of a 46 years-old man with spontaneous carotid artery dissection that had an atypical manifestation characterized by sudden paralysis of lower cranial nerves.

[Evaluation of body weight in patients with Graves' disease during the treatment with methimazole]. / Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol.

OBJECTIVE: To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations. SUBJECTS AND METHODS: Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism. RESULTS: BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m(2) to 27 kg/m(2) ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m(2) and 33.3%, BMI > 25 kg/m(2). In euthyroidism, 38% of patients had BMI < 25 kg/m(2) and 62%, BMI > 25 kg/m(2) (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI. CONCLUSION: An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol / Evaluation of body weight in patients with Graves' disease during the treatment with methimazole

OBJETIVO: Avaliar a alteração de peso durante o tratamento do hipertiroidismo e correlacioná-la com IL-6 e TNF-alfa. SUJEITOS E MÉTODOS: Quarenta e dois pacientes foram incluídos. Peso corporal (PC), índice de massa corpórea (IMC), características clínicas e laboratoriais foram registrados. IL-6 e TNF-alfa foram determinados antes do tratamento com metimazol (MMI) e no estado de eutiroidismo. RESULTADOS: O PC foi de 59,62 ± 11,5 kg no estado de hipertiroidismo e de 69,91 ± 14,4 kg no estado de eutiroidismo (p < 0,001). O IMC aumentou de 23,1 ± 3,8 kg/m² para 27 ± 4,7 kg/m² durante o tratamento (p < 0,0001). Antes da terapia, 66,6% tinham IMC < 25 kg/m² e 33,3%, IMC > 25 kg/m². No estado de eutiroidismo, 38% dos pacientes apresentavam IMC < 25 kg/m² e 62%, IMC > 25 kg/m² (p = 0,01). No estado de eutiroidismo, encontrou-se significativa diminuição nos valores de IL-6 e TNF-alfa, mas nenhuma correlação entre IL-6 e TNF-alfa com PC ou IMC. CONCLUSÃO: Um importante aumento no PC e IMC foi observado durante o tratamento do hipertiroidismo e alterações de IL-6 e TNF-alfa relacionam-se somente com o retorno ao eutiroidismo.

OBJECTIVE: To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations. SUBJECTS AND METHODS: Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism. RESULTS: BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m² to 27 kg/m² ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m² and 33.3%, BMI > 25 kg/m². In euthyroidism, 38% of patients had BMI < 25 kg/m² and 62%, BMI > 25 kg/m² (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI. CONCLUSION: An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Dissecção espontânea de artéria carótida interna com paralisia de nervos cranianos inferiores: relato de caso / Spontaneous internal carotid artery dissection with paralysis of lower cranial nerves: case report

A dissecção espontânea da artéria carótida interna é evento raro, acometendo principalmente indivíduos em idade produtiva. Como a abordagem precoce e adequada dessa doença determina quase sempre melhora significativa, torna-se evidente a necessidade de ampliar os conhecimentos sobre seus aspectos clínicos, patogênicos e fisiopatológicos, visando o diagnóstico e tratamento precoces, bem como a redução de suas possíveis seqüelas. Pelos motivos expostos, julgamos pertinente relatar o caso de um homem de 46 anos com dissecção espontânea de artéria carótida interna, com manifestações clínicas atípicas dentre as quais ressaltamos a paralisia de nervos cranianos inferiores.

Spontaneous internal carotid artery dissection is a rare event that strikes patients at their productive age. As early intervention frequently determines a significant improvement, it is important to broaden the knowledge of the clinical, pathogenic and pathophysiological aspects of this disease. The objective is making an early diagnosis and treatment to avoid a bad outcome. We report the case of a 46 years-old man with spontaneous carotid artery dissection that had an atypical manifestation characterized by sudden paralysis of lower cranial nerves.