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The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1\u201367\u2009years) with suspected or known primary PN and\/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate \u2265100\u2009mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1\/100 of their individual threshold, increasing the protein amount to 1\/50 and 1\/10 after 4 and 8\u2009months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and\/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and\/or TN after 1 year assessed by challenging with the former tolerated cumulative dose.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>German Clinical Trials Register; ID: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.drks.de\/drks_web\/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS00016764\">DRKS00016764<\/jats:ext-link> (RCT), <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.drks.de\/drks_web\/navigate.do?navigationId=trial.HTML&amp;TRIAL_ID=DRKS0002046\">DRKS00020467<\/jats:ext-link> (cohort study). Registered on 15 January 2020, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.drks.de\">http:\/\/www.drks.de<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-022-06149-4","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T02:04:48Z","timestamp":1648519488000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study"],"prefix":"10.1186","volume":"23","author":[{"given":"Val\u00e9rie","family":"Trendelenburg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"D\u00f6lle-Bierke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Unterleider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aikaterina","family":"Alexiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Kalb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara","family":"Meixner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Heller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young- Ae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florent","family":"Fauch\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Braun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magda","family":"Babina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Altrichter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"Birkner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Roll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josefine","family":"Dobbertin-Welsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margitta","family":"Worm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-0419","authenticated-orcid":false,"given":"Kirsten","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"issue":"3","key":"6149_CR1","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.jaci.2007.05.026","volume":"120","author":"RJ Rona","year":"2007","unstructured":"Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. 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Any substantial amendments to the protocol or to the consent materials must also be approved by the Ethics Committee of Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin before implementation.All participants (means participants or participant or parent\/legal guardian according to age) give their full consent before they or their children are enrolled into the trial. The informed consent form must be revised whenever important new safety information is available, whenever the protocol is amended leading to changes in study procedures relevant for the patient, and\/or whenever any new information becomes available that may affect participation in the trial.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"VT received speaker\u2019s fees from Nutricia\/Danone. Kirsten Beyer reports grants\/research supports from Aimmune, Danone\/Nutricia\/Milupa, DBV, Hipp, Hycor, Infectopharm, and honoraria or consultation fees from Aimmune, Bencard, Danone\/Nutricia\/Milupa, DBV, Hipp, Hycor, Infectopharm, Jenapharma, Mylan\/Meda, Nestle, Novartis, and ThermoFisher outside of the submitted work. Margitta Worm declares the receipt of honoraria or consultation fees by the following companies: ALK-Abell\u00f3 Arzneimittel GmbH, Mylan Germany GmbH, Leo Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Regeneron Pharmaceuticals, DBV Technologies S.A, Stallergenes GmbH, HAL Allergie GmbH, Allergopharma GmbH & Co. KG, Bencard Allergie GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG, Biotest AG., AbbVie Deutschland GmbH & Co. KG, and Lilly Deutschland GmbH. All other authors report that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"236"}}