Filip Scheperjans, Reeta Levo, Berta Bosch, Mitja Lääperi, Pedro A B Pereira, Olli-Pekka Smolander, Velma T E Aho, Nora Vetkas, Lotta Toivio, Veera Kainulainen, Tatyana D Fedorova, Perttu Lahtinen, Rebekka Ortiz, Valtteri Kaasinen, Reetta Satokari, Perttu Arkkila
{"title":"粪便微生物群移植治疗帕金森病：随机临床试验","authors":"Filip Scheperjans, Reeta Levo, Berta Bosch, Mitja Lääperi, Pedro A B Pereira, Olli-Pekka Smolander, Velma T E Aho, Nora Vetkas, Lotta Toivio, Veera Kainulainen, Tatyana D Fedorova, Perttu Lahtinen, Rebekka Ortiz, Valtteri Kaasinen, Reetta Satokari, Perttu Arkkila","doi":"10.1001/jamaneurol.2024.2305","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.</p><p><strong>Objective: </strong>To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.</p><p><strong>Design, setting, and participants: </strong>This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.</p><p><strong>Intervention: </strong>Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.</p><p><strong>Main outcomes and measures: </strong>The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).</p><p><strong>Results: </strong>The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.</p><p><strong>Conclusions and relevance: </strong>FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04854291.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"925-938"},"PeriodicalIF":20.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287445/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.\",\"authors\":\"Filip Scheperjans, Reeta Levo, Berta Bosch, Mitja Lääperi, Pedro A B Pereira, Olli-Pekka Smolander, Velma T E Aho, Nora Vetkas, Lotta Toivio, Veera Kainulainen, Tatyana D Fedorova, Perttu Lahtinen, Rebekka Ortiz, Valtteri Kaasinen, Reetta Satokari, Perttu Arkkila\",\"doi\":\"10.1001/jamaneurol.2024.2305\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.</p><p><strong>Objective: </strong>To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.</p><p><strong>Design, setting, and participants: </strong>This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.</p><p><strong>Intervention: </strong>Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.</p><p><strong>Main outcomes and measures: </strong>The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).</p><p><strong>Results: </strong>The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.</p><p><strong>Conclusions and relevance: </strong>FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04854291.</p>\",\"PeriodicalId\":14677,\"journal\":{\"name\":\"JAMA neurology\",\"volume\":\" \",\"pages\":\"925-938\"},\"PeriodicalIF\":20.4000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287445/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAMA neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamaneurol.2024.2305\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamaneurol.2024.2305","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.
Importance: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.
Objective: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.
Design, setting, and participants: This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.
Intervention: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.
Main outcomes and measures: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).
Results: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.
Conclusions and relevance: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.
期刊介绍：
JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.
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