What large-scale, multi-site randomized trials of rTMS for tinnitus are currently registered or underway?
Executive summary
The evidence landscape for repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus has long been marked by small, heterogeneous studies and repeated calls for large, multi‑site randomized trials; the reporting in these sources identifies a handful of multicenter randomized protocols and two large trials that have driven the field’s debate, but the available documents do not present a contemporary registry roster of active, ongoing large multi‑site trials [1] [2] [3]. What can be stated from the provided material is which large, multicenter randomized trials were planned, registered, or published and where gaps in the record prevent asserting that particular trials are currently open and recruiting. [4] [5] [6]
1. Large, multicenter randomized trials that shaped the debate
Two large randomized clinical trials are repeatedly cited as the pivotal multicenter studies whose differing outcomes have animated controversy: Folmer et al.’s randomized clinical trial and the multicenter 1‑Hz rTMS trial led by Landgrebe et al., both of which are discussed as large‑scale randomized studies in systematic reviews and reviews of the literature [6] [3]. Systematic reviewers point to these two trials as having “almost identical methodological design and different reported results,” underlining why the field demands further well‑powered, multisite replication [3].
2. Registered multicenter protocols and trial registrations identified in reporting
Earlier efforts to move beyond single‑center pilot work produced explicit multicenter trial registrations and study protocols: a randomized, placebo‑controlled, double‑blind multi‑center trial was registered as ISRCTN89848288 with a published design paper describing a two‑week 1‑Hz rTMS vs sham protocol intended for a large sample of chronic tinnitus patients [4]. Another registered trial protocol compared single‑site versus multisite rTMS and was registered on ClinicalTrials.gov as NCT01663324; that protocol defined a randomized, double‑blind, parallel‑group multicenter study targeting frontoparietal network nodes in addition to auditory cortex areas [5].
3. Multisite pilot and novel multisite designs in the literature
Prior multisite pilot work and trials testing multi‑site targeting strategies have also been published: Lehner and colleagues reported multisite rTMS approaches in pilot and randomized formats (including a triple‑site randomized controlled trial published in Scientific Reports) that experimentally targeted multiple network nodes rather than a single auditory cortical site [7] [8]. These studies represent attempts to scale up and diversify stimulation targets across centers but are described as pilot or randomized trials rather than necessarily meeting a criterion of large‑scale, definitive multicenter phase‑III status in the provided sources [7] [8].
4. Why reviewers continue to call for new large multi‑site RCTs
Multiple systematic reviews and meta‑analyses note persistent heterogeneity in protocols, small overall sample sizes despite dozens of randomized trials (29 trials and 1,228 patients in one meta‑analysis), and at least one large multicenter negative trial that tempered enthusiasm—leading authors to repeatedly recommend additional large, double‑blind, multicenter trials to define optimal parameters, targets, and patient selection [9] [10] [11] [1]. The MDPI review explicitly lists unresolved technical and population issues and states that large‑scale, multi‑site trials are needed to determine which rTMS protocols are most effective [2].
5. Limits of the available reporting and what remains unknown
The sources supplied identify specific multicenter protocols (ISRCTN89848288, NCT01663324), major published multicenter trials (Landgrebe et al., Folmer et al.), and multisite pilot/randomized studies (Lehner triple‑site work), but they do not provide a contemporaneous registry query or list of trials that are currently active, recruiting, or underway as of January 2026; therefore it cannot be asserted from these documents which large multi‑site rTMS tinnitus trials remain open now without fresh registry searches beyond the provided materials [4] [5] [6] [7] [8] [2]. Reviewers and trialists in the literature explicitly demand more large, multicenter randomized trials, which indicates both the existence of prior multicenter attempts and the perceived insufficiency of the evidence base to date [1] [2].