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Lower prevalence of inflammatory and metabolic diseases such as T2DM in countries with higher incidences of helminth infections suggested a potential role for these parasites in the prevention and management of certain diseases. Recent studies confirmed the potential protective nature of helminth infection against MetS and T2DM via immunomodulation or, potentially, alteration of the intestinal microbiota. This Phase 1b safety and tolerability trial aims to assess the effect of inoculation with helminths on physical and metabolic parameters, immune responses, and the microbiome in otherwise healthy women and men.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Participants eligible for inclusion are adults aged 18\u201350 with central obesity and a minimum of one additional feature of MetS recruited from the local community with a recruitment target of 54. In a randomised, double-blind, placebo-controlled design, three groups will receive either 20 or 40 stage three larvae of the human hookworm <jats:italic>Necator americanus<\/jats:italic> or a placebo. Eligible participants will provide blood and faecal samples at their baseline and 6-monthly assessment visits for a total of 24\u2009months with an optional extension to 36\u2009months. During each scheduled visit, participants will also undergo a full physical examination and complete diet (PREDIMED), physical activity, and patient health (PHQ-9) questionnaires. Outcome measurements include tolerability and safety of infection with <jats:italic>Necator americanus<\/jats:italic>, changes in metabolic and immunological parameters, and changes in the composition of the faecal microbiome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Rising cost of healthcare associated with obesity-induced metabolic diseases urgently calls for new approaches in disease prevention. Findings from this trial will provide valuable information regarding the potential mechanisms by which hookworms, potentially via alterations in the microbiota, may positively influence metabolic health.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>The protocol was registered on <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/anzctr.org.au\">ANZCTR.org.au<\/jats:ext-link> on 05 June 2017 with identifier <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=372957&amp;isReview=true\">ACTRN12617000818336<\/jats:ext-link>.<\/jats:p>\n                <jats:p>Alternatively, a Google search using the above trial registration number will yield a direct link to the trial protocol within the ANZCTR website.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-019-0461-5","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T14:07:10Z","timestamp":1576073230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Safety and tolerability of experimental hookworm infection in humans with metabolic disease: study protocol for a phase 1b randomised controlled clinical trial"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-1218","authenticated-orcid":false,"given":"Doris","family":"Pierce","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Merone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Croese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Giacomin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"issue":"10159","key":"461_CR1","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/S0140-6736(18)32225-6","volume":"392","author":"JD Stanaway","year":"2018","unstructured":"Stanaway JD, Afshin A, Gakidou E, Lim SS, Abate D, Abate KH, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, et al. 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Important protocol modifications will be communicated to all investigators, JCU\u2019s Human Ethics Research Committee, and trial registries. Should these modifications impact on already recruited participants, renewed informed consent will be obtained, as required.Prior to any eligibility assessment, the study doctor will obtain written informed consent from potential participants after all open questions have been clarified, and the volunteer agrees to participate. Participants can withdraw from the trial at any time without providing reasons. In case of withdrawal, participants will be scheduled for an Early Termination Visit for final health assessments. Data collected prior to and during the Early Termination Visit will form part of the study results (identification number removed).The study is not expected to involve any substantial risk or cost to the participants; therefore, volunteers will not receive financial compensation for participation in this trial. However, participants will be reimbursed for the cost of any reasonable travel or parking cost associated with the study visits.The study doctors, nurses and scientists will receive no payment from the Sponsor or their institutions for undertaking this research study (other than their ordinary wages). No member of the research team will receive a personal financial benefit from involvement in this study (other than their ordinary wages).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors currently have no competing interests to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"136"}}