This project aims to investigate the effect of adjunctive noninvasive brain stimulation on speech fluency. To this aim, we will recruit 2 groups of participants—an intervention group and a control group. In the intervention group, participants will receive anodal tDCS simultaneously with DAF as a fluency intervention, whereas the participants in the control group will receive sham stimulation during DAF. The population of this study will be adults with a stutter. We hypothesize that anodal tDCS over the temporal target area will improve the efficacy of DAF to enhance speech fluency and will stabilize treatment effects.

We hypothesize that the efficacy of the intervention to enhance fluency of speech in individuals with a stutter is improved when combined with anodal tDCS over the superior temporal gyrus, as compared to a sham tDCS control condition.

The primary objective of this proposal is to compare the mean score of the percentage of stuttered syllables (SS%) [17] between the intervention and control groups at 5 time points: 1 week before treatment; immediately before treatment; and immediately, 1 week, and 6 weeks after treatment.

The secondary objectives are as follows:

We expect adjunctive tDCS to enhance the magnitude of the effects of the intervention on our outcome parameters and to enhance the stability of improvements made due to the treatment.

There is no anticipated relevant risk associated with the stimulation parameters used in this study [20]. In a systematic review evaluating adverse effects of all published tDCS studies, including studies conducted in vulnerable populations, adverse effects of tDCS such as tingling and itching sensations under the electrodes were mild and disappeared soon after stimulation. No severe adverse effects of tDCS have been documented so far. It thus can be concluded that tDCS within the proposed stimulation parameters is safe [21].

The study population will include adults with moderate-to-severe stuttering who have not received any treatment at least 1 month prior to the intervention. A speech-language pathologist will assess the severity of stuttering in each subject to determine whether he or she can be enrolled. The SSI-4 questionnaire will be used to assess stuttering severity. Inclusion, exclusion, and withdrawal criteria are listed in Textbox 1.

This study is designed as a randomized, double-blind, sham-controlled clinical trial. Participants will be randomly allocated to a control or intervention group. All participants will receive DAF during the intervention. The intervention group will additionally receive anodal tDCS, while the control group is exposed to sham tDCS. Data will be collected via questionnaires, voice recordings, and observations at 5 time points (ie, 1 week and immediately before the intervention; and immediately, 1 week, and 6 weeks post intervention). By comparing the outcomes of the respective treatments, we will investigate the efficacy of anodal tDCS combined with DAF in enhancing speech fluency.

Before starting the treatment program, 2 preintervention assessments will be conducted to determine the severity of stuttering. Once these assessments are completed, each subject will participate in 6 intervention sessions. Postintervention assessments will be carried out immediately and 1 week after the last intervention session. Afterward, to explore the long-term stability of the treatment results, the outcome parameters will be obtained in follow-up assessments 6 weeks after the treatment. This single-center trial will be conducted at the Vahdat Neurorehabilitation Clinic in Tehran, Iran.

As previously mentioned, the study will be conducted on adults with moderate-to-severe stuttering; hence, prior to recruitment, the severity of stuttering will be assessed to determine enrollment eligibility. In order to determine the severity of stuttering, an SSI-4 score for each individual will be calculated.

We will obtain two baseline measurements—one at 1 week and the other immediately before the intervention—to guarantee symptom stability. At baseline, the participants will be visited individually, and their voices will be recorded while performing 3 different tasks (ie, oral reading, monologue, and conversation). Based on these data, we will calculate the primary outcome measure (ie, SS%). The voice of the participants will be recorded by a H5 Handy Recorder ZOOM). Two experienced specialist raters will independently count the SS% of all speech samples. In order to determine interrater reliability, Cohen kappa will be calculated. In cases of agreement between the raters (intraclass correlation coefficient=0.8-1), the SS% will be reported. In cases of disagreement (intraclass correlation coefficient <0.8), a third senior rater will evaluate SS%.

During the two baseline sessions, the principal investigator will observe physical behavior, which is required to calculate the SSI-4 score. The final part of the preintervention assessments is the completion of the OASES questionnaire by the participants. After the second baseline assessment, the intervention will start and carry on for 6 consecutive days.

At 3 time points after the last intervention session (ie, immediately, 1 week, and 6 weeks), each subject will undergo postintervention assessments, which will be identical to the preintervention assessments and obtained by the same raters. The trial design and timeline are shown in Figure 1.

After each intervention session, participants will fill out a questionnaire using a 5-point Likert scale (1=very mild, 5=very severe) to report potential side effects of tDCS, including itching, burning, tingling, headache, fatigue, sudden mood change, difficulties in concentration, changes in visual perception, unpleasant somatosensory sensations, unpleasant visual sensations, nausea, drowsiness, persisting feelings of stimulation, and 1 open question for any other adverse effects.

In addition, to ensure successful blinding, participants will be asked to guess the type of treatment they will or had received (ie, anodal tDCS or sham) before and after the intervention.

This study is a randomized, double-blind, sham-controlled trial. Participants will be randomly allocated to the intervention and control groups. The random assignment of participants ensures the prevention of a possible selection bias and a disbalance of confounding factors between the study arms. Randomization will be performed via a web-based randomization tool [22]. In accordance with the requirements of this tool, we will include 50 subjects and 4 blocks of equal size, for which randomization will be performed independently. Each subject will be given an ID number and will be assigned to one of the treatment groups. The individual responsible for generating the random list will not be involved in any other part of the trial.

As the study is double-blinded, neither the participants nor the investigators will know which group each participant will be assigned to. Sealed opaque envelopes will be used for concealment. Accordingly, an envelope will be produced for each subject. These envelopes will be marked with an ID number, and the treatment group associated with each ID will be placed in its respective envelope. In order to guarantee double blinding, specific letters, unknown to the principal investigator and the subjects, will be used instead of the actual names of the treatment groups (ie, intervention and control) inside the envelopes. Assignment of these letters to the respective intervention group will be done by a clinician (not the principal investigator). Before the principal investigator starts the treatment of the respective participant, the subject will be given one of the sealed envelopes by the clinician. Once the envelope is opened by the corresponding participant, the clinician will set up the mode—anodal or sham—based on the content of the subject's envelope and attach the electrodes to the participant´s head as illustrated in the sections below. Once completed, the principal investigator will commence the treatment. The researchers who are responsible for outcome assessment and data analysis will also be blinded to the intervention groups.

In this proposal, the null hypothesis (H₀) is that the combined treatment method using tDCS stimulation and DAF, as compared to DAF combined with sham stimulation, has no additional effect on the enhancement of speech fluency in adults who stutter.

This study will be carried out in accordance to the ethical principles and national norms and standards for conducting medical research in Iran (approval ID: IR.IUMS.REC.1398.352, Iran National Committee for Ethics in Biomedical Research). In addition, our informed consent form will be reviewed and approved by the ethics committee. Prior to the commencement of any part of the study, the principal investigator will obtain written informed consent from all participants.

All study findings and information will be posted on ClinicalTrials.gov (identifier NCT03990168). Although the investigator will be free to use the study findings for educational and scientific purposes, written consent will be obtained from the study sponsor prior to submission of any manuscript for publication.

Information about subjects will be kept confidential and will not be available for public access. In addition, any document, data, voice recording, and other records will be identified by a participant ID number, and the name of each subject will be kept confidential. The data sets used and analyzed during the study are available from the corresponding author upon reasonable request.