scholarly journals Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e048541
Author(s):  
Anna-Maria Hoffmann-Vold ◽  
Håvard H Fretheim ◽  
Vikas K Sarna ◽  
Imon Barua ◽  
Maylen N Carstens ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pilot Study ◽  
Phase Ii ◽  
Intestinal Microbiome ◽  
Induction Phase ◽  
Inflammatory Disorder ◽  
Faecal Microbiota ◽  
Safety And Efficacy ◽  
Faecal Microbiota Transplantation ◽  
Patient Reported

IntroductionIn the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture ‘Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)’. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc.Methods and analysesWe aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating).Ethics and disseminationThis protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published.Trial registration numberNCT04300426; Pre-results.Protocol versionV.3.1.

scholarly journals AB0433 STUDY DESIGN FOR THE RANDOMISED CONTROLLED PHASE II ReSScue TRIAL: SAFETY AND EFFICACY OF FAECAL MICROBIOTA TRANSPLANTATION BY ANAEROBIC CULTIVATED HUMAN INTESTINAL MICROBIOME (ACHIM) IN PATIENTS WITH SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1245.2-1246
Author(s):  
H. Fretheim ◽  
I. Barua ◽  
V. Sarna ◽  
M. N. Carstens ◽  
O. Distler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Medical Officer ◽  
Intestinal Microbiome ◽  
Feasibility Trial ◽  
Faecal Microbiota ◽  
Research Support ◽  
Safety And Efficacy ◽  
Faecal Microbiota Transplantation

Background:Gastro-intestinal tract (GIT) symptoms is highly prevalent in patients with systemic sclerosis (SSc). The GIT-symptoms impact on the quality of life is significant, and available treatment alternatives are limited. Recently published articles show associations between gut microbiota changes and GIT-symptoms in SSc. We, therefore, performed a successful feasibility trial on faecal microbiota transplantation (FMT) in SSc patients using the single-donor bacterial culture “Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)”. Based on the promising results from the feasibility trial, we aim to evaluate the safety and efficacy of FMT by ACHIM in SSc patients. (NCT04300426)Objectives:To design a clinical trial that explores the safety and efficacy of FMT in SSc patients.Methods:The ReSScue trial is a phase II, placebo-controlled, randomised 20-week, multicentre trial. The trial comprises three parts. In the induction phase (A1) lasting from week 0 to week 12, participants are randomised 1:1 to repeat infusions of 30 ml ACHIM or placebo at week 0 and 2 by gastro-duodenoscopy. In the maintenance phase (A2), all study participants will receive 30 ml ACHIM at week 12 and are followed continued blinded until week 20.For longer-term data on intervention effects and safety, the participant will be followed for a maximum extended monitoring period of 16 weeks (part B).The primary endpoint is change from baseline to week 12 in UCLA GIT scores on bloating or diarrhoea, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are changes in UCLA GIT scores (bloating, diarrhoea and total) and safety measures.Results:We aim to enrol 70 SSc patients based on the power calculations for the primary endpoint “change in worst symptom from baseline to week 12”, with a considered drop out rate of 10%. This number of patients is expected to give a power of 80% of detecting a change in mean (p=0.05, two-sided) of -5.0 (or higher) if the relating standard deviation is 0.70 or lower. The patient screening started in September 2020, and we expect the study to be completed in May 2022.Conclusion:The ReSScue-study is to our knowledge the first FMT-study in SSc. This trial will assess the safety and efficacy of FMT in SSc patients with lower GI-symptoms, possibly leading to a novel treatment approach in SSc patients.Disclosure of Interests:Håvard Fretheim Grant/research support from: Received travel bursaries from Actelion, and remuneration from Bayer., Imon Barua: None declared, Vikas Sarna: None declared, Maylen N Carstens: None declared, Oliver Distler Speakers bureau: Below, Consultant of: Below, Grant/research support from: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx, Baecon Discovery, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, iQone, Kymera, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Dinesh Khanna Consultant of: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Grant/research support from: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Boehringer Ingelheim, Øyvind Midtvedt Shareholder of: Son of owner of ACHIM., Henriette Didriksen Speakers bureau: Travel bursary - GSK, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge Christoffer Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche., Grant/research support from: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche.

Sa1922 Pilot Study on the Safety and Efficacy of Faecal Microbiota Transplantation in Refractory Crohn's Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-360 ◽  
Author(s):  
Severine Vermeire ◽  
Marie Joossens ◽  
Kristin Verbeke ◽  
Falk Hildebrand ◽  
Kathleen Machiels ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Pilot Study ◽  
Crohn's Disease ◽  
Faecal Microbiota ◽  
Safety And Efficacy ◽  
Faecal Microbiota Transplantation

Faecal microbiota transplantation to chronic pouchitis improves quality of life: a pilot study

2020 ◽  
Vol 35 (11) ◽  
pp. 2135-2136
Author(s):  
Sabrina Just Kousgaard ◽  
Hans Linde Nielsen ◽  
Karina Frahm Kirk ◽  
Ole Thorlacius-Ussing
Keyword(s):  
Quality Of Life ◽  
Pilot Study ◽  
Faecal Microbiota ◽  
Faecal Microbiota Transplantation

scholarly journals Safety and Efficacy of Lenabasum in a Phase II, Randomized, Placebo‐Controlled Trial in Adults With Systemic Sclerosis

2020 ◽  
Vol 72 (8) ◽  
pp. 1350-1360 ◽  
Author(s):  
Robert Spiera ◽  
Laura Hummers ◽  
Lorinda Chung ◽  
Tracy M. Frech ◽  
Robyn Domsic ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety And Efficacy

A phase II study of loratidine (L) and naproxen (N) to prevent pegfilgrastim-induced pain (PIP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19510-e19510 ◽  
Author(s):  
Jeffrey J. Kirshner ◽  
Charles E Heckler ◽  
Carol Reichel ◽  
Gary R. Morrow
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Phase Ii ◽  
Initial Dose ◽  
Severe Pain ◽  
Phase Ii Study ◽  
Eligibility Criteria ◽  
Pilot Studies ◽  
Safety And Efficacy ◽  
Present Pilot Study

e19510 Background: We have previously demonstrated the efficacy of N in terms of preventing the incidence, severity and duration of PIP (ASCO 2010; JCO, in press). Last year at ASCO, we reported the results of a pilot study of L, using similar methodology. The present pilot study was designed to determine the safety and efficacy of the combination of N + L , used to prevent PIP. Methods: Using identical eligibility criteria to the aforementioned studies, 41 pts were treated with N 500 mg po bid and L 10 mg po qd beginning on the morning of their initial dose of P and continuing for 5-8 days. Pain at any time was recorded by pts in diaries using a 0-10 scale. Unexpected adverse events were promptly reported. Similar methodology and statistical analyses were used, with the primary endpoint being AUC for the severity and duration of pain. Results: Six pts either did not take the pills or return questionnaires. 35 evaluable pts were treated (27F;8M). Cancers included 24 breast, 7 lung and 4 others. AUC was 7.10. At any time during the 5 days after administration of P, 10 pts experienced no pain, 17 had some mild pain and 8 had some severe pain. No unexpected adverse events were reported. Comparison to our prior studies is tabulated (see table below). Conclusions: The combination of N + L does not appear to be unsafe when used to prevent PIP, but in these small pilot studies, the regimen does not appear to be any more efficacious than either drug when used alone. A larger study is needed to specifically evaluate efficacy and toxicity. [Table: see text]

scholarly journals Evaluation of the safety and efficacy of TY-51924 in patients with ST elevated acute myocardial infarction – Early phase II first in patient pilot study

2016 ◽  
Vol 67 (2) ◽  
pp. 162-169 ◽  
Author(s):  
Tadateru Takayama ◽  
Kazuo Kimura ◽  
Shigeru Fukuzawa ◽  
Haruo Hirayama ◽  
Takahito Sone ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Pilot Study ◽  
Phase Ii ◽  
Early Phase ◽  
Safety And Efficacy

scholarly journals Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial

2021 ◽  
pp. annrheumdis-2020-219511
Author(s):  
Maja Skov Kragsnaes ◽  
Jens Kjeldsen ◽  
Hans Christian Horn ◽  
Heidi Lausten Munk ◽  
Jens Kristian Pedersen ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Treatment Failure ◽  
Controlled Trial ◽  
Faecal Microbiota ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response ◽  
Safety And Efficacy ◽  
Faecal Microbiota Transplantation

ObjectivesAlthough causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).MethodsIn this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.ResultsOf 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).ConclusionsIn this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.Trial registration numberNCT03058900.

scholarly journals Safety and Efficacy of an Atraumatic Uterine Cervical Traction Device: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Hélène Legardeur ◽  
Gessica Masiello-Fonjallaz ◽  
Martine Jacot-Guillarmod ◽  
Patrice Mathevet
Keyword(s):  
Pilot Study ◽  
Contraceptive Device ◽  
Clinical Trial Registration ◽  
Safety And Efficacy ◽  
Patient Reported ◽  
Intrauterine Contraceptive ◽  
Cervical Traction ◽  
Traction Device ◽  
Study Support ◽  
Vaginal Canal

Introduction: Alignment of the uterine cervix with the vaginal canal is often required during insertion of an intrauterine contraceptive device (IUD). Currently available instruments are traumatic tenacula, which can cause pain and bleeding and represent an obstacle for certain patients to pursue their medical follow-up. A novel investigational cervical vacuum tenaculum, enables atraumatic traction of the cervix using a semi-circular suction pad, designed to conform to the anatomical shape of the external cervical os. Suction is generated by manually pulling out a sliding tube in a vacuum chamber.Methods: We performed a single arm non-comparative pilot study to assess the safety and efficacy of the cervical vacuum tenaculum in 13 women receiving an IUD. Data on procedural efficacy, safety, patient-reported pain scores at specific time points during IUD insertion procedure and patient satisfaction were collected prospectively.Results: Insertion of IUD was successful with use of the study device in 7 of the 13 enrolled patients (54%). No bleeding or only limited ecchymosis were caused by the device. No adverse events were reported. Participants reported very little pain (mean Visual Analog Scale <10) when applying the device. Participants who achieved IUD insertion with the device reported strong overall satisfaction with the procedure.Conclusions: The suction-based atraumatic tenaculum can be used to manipulate the cervix during IUD insertion with satisfactory efficacy and safety. The results of this pilot study support further studies of this device in larger populations comparing with standard single-tooth tenaculum.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT 04441333.

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