A chronic protocol of bilateral transcranial direct current stimulation over auditory cortex for tinnitus treatment: Dataset from a double-blinded randomized controlled trial

Participants and dataset schema

This dataset presents the results of a double blinded randomized placebo controlled clinical trial investigated the effects of chronic protocol of bilateral tDCS over AC in intractable chronic tinnitus (n=40)¹⁸. It should be noted that the main study protocol was designed with three arms (anode, cathode, and placebo, each with 30 patients)¹⁸. However, due to several reasons we decided to conduct and report the results of the two arms of the protocol as a separate study. The two arms were anode (real group) and placebo groups. The remaining arms of the original study are under recruitment phase and will be conducted with two arms of cathode (n=30) and placebo (n=30). The main reason was difficulty in recruiting enough patients who meet the inclusion/exclusion criteria so that we could not conduct the whole study as a single trial within a season, and the duration of the study took a long time. In addition, we observed a significant different therapeutic outcomes between the real (anode arm) and placebo groups and decided to report the two arms as a separate study. The primary outcomes of this study are expected to be reported within approximately 4 months.

The data consist of three main groups: the first group is demographic information, tinnitus characteristics and audiometric assessments of the patients; the second group are data of the primary and secondary outcomes at pre- and post-intervention; and the third group are data concerning the adverse effects and tolerability of tDCS. Table 1 presents the demographic information, tinnitus characteristics (including tinnitus quality, laterality and duration), audiometric assessments, and the primary and secondary outcomes for pre- and post-intervention for the participants in the real tDCS. The corresponding data for the sham tDCS group are presented in Table 2. Table 3 and Table 4, respectively, present the adverse effects and tolerability of tDCS for real and sham tDCS groups using a customized questionnaire (Supplementary File 1).

Study design

All of the experimental procedures of the study were approved by local ethical committee of Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran (registration code: IR.AJUMS.REC.1394.639), and were completely in accordance with the ethical standards and regulations of human studies of the Helsinki declaration (2014). After the enrolment, objectives, possible benefits, and side effects of the study were clearly explained to the patients and all patients filled and signed a written consent form for participation in the study.

Patients with intractable chronic tinnitus (n=40) were randomly assigned into real tDCS (n=25; female, 14; male, 11; age, 47.52 ± 7.51 years; disease duration, 7.48 ± 3.99 years) and placebo tDCS (n=15; female, 8; male, 7; age, 47.67 ± 7.96 years; disease duration, 7.60 ± 3.60 years) in a parallel allocation and a double-blinded randomized controlled clinical trial (Figure 1). Due to the difficulty in the patient recruitment and high number of the patients who did not complete the treatment we reduced the size in the anode and placebo group (n=25 vs n=30 for the anode group and n=15 vs n=30 for the placebo group). The change in the groups’ size was approved by the local ethics committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (registration code: IR.AJUMS.REC.1394.639). The treatment consisted of daily sessions of 20 minutes of 2 mA current for 5 consecutive days per week and 2 consecutive weeks with 35 cm² electrodes. Both groups were matched in age, gender, ethnicity, and audiometric main characteristics. The patients, the researcher who evaluated the outcomes during the experiments and at the follow-up period, and the researchers who performed data analyses were blinded to the type of protocol. The experimental procedures of the present study, including tDCS sessions and outcomes evaluations, were performed at the Bioelectromagnetic Clinic in Ahvaz Imam Hospital, an affiliated Hospital to AJUMS, Iran. The study was registered as a clinical trial in the Iranian Registry of Clinical Trial (IRCT2016110124635N6), which is the registration for the original clinical trial design¹⁸.

Figure 1. CONSORT diagram of the study.

TDCS intervention

The direct current was applied through a saline-soaked pair of carbon electrodes (35 cm²) and delivered by a tDCS device (OASIS Pro^TM; Mind Alive, Inc., Edmonton, Alberta, Canada). The tDCS protocol consisted of 2 mA current, daily for 20 min, over 5 consecutive days per week for 2 consecutive weeks (total, 10 sessions). The anode was placed over left AC (halfway T3 - F7) and cathode over right AC (halfway T4 - F8) with 35 cm² electrodes. In the placebo tDCS, the electrode montage was the same with real tDCS except that the device was turned off after 30 s after the start of session without the patient knowing it¹⁹. During treatment, the patients were asked to remove all metal-based jewelry from the head and neck.

Clinical evaluation

Before the start of the first session of tDCS, intervention, all patients underwent complete audiometric and neurological assessments by expert specialties and the data were recorded along with the demographic data (Table 1 and Table 2). The recorded variables consisted of the tinnitus quality, lateralization, duration, and class of hearing loss in both ears (Table 1 and Table 2). The lateralization or tinnitus side is the dominant side of the head where the patient experiences the tinnitus and was classified as left (L), right (R), bilateral with no lateralization (R = L), bilateral lateralizing more to the right side (R>L), bilateral lateralizing more to the left side (L>R). In addition, hearing assessments were conducted in an acoustically isolated chamber with pure-tone audiometry using an AC 40 dual-channel Audiometer (Intracoustics Co., Denmark). The hearing thresholds were recorded over the frequency ranges of 250 to 8000 Hz for air conduction and 500 to 4000 Hz for bone conduction pathways, according to the modified Hughson–Westlake Method proposed by ANSI 1997²⁰. Pure-tone audiometry was considered normal whenever the hearing thresholds at all frequencies were below 20 decibels hearing level (dBHL). The class of hearing loss in both ears was classified as normal hearing threshold (<20 dB), mild hearing loss (20–40 dB), moderate hearing loss (41–70 dB), severe hearing loss (70–90 db), and profound hearing loss (>90 db). The hearing class was determined as the average of threshold in 250, 1000, 2000, and 4000 Hz²⁰. The THI scores were assessed at pre-intervention, immediately after intervention, and at 1 month after the last stimulation. The tinnitus loudness and distress were recorded using a numeral 0–10 VAS rating scale before intervention, and immediately, 1 hour, 1 week, and 1 month after last stimulation.

Adverse effects and tolerability

Previous studies have demonstrated that tDCS is relatively safe with no serious side effects^11,15,19. It should be mentioned that most of the conducted studies on the safety profile of tDCS assessed during single-session tDCS with different current intensities. For this study, considering the chronic protocol of tDCS, the adverse effects of and tolerability to the chronic protocol of tDCS were assessed using a customized questionnaire (Supplementary File 1). We used a five-point Likert-type scale for each adverse effect and the tolerability. In addition, the site (under cathode, under anode, other (mention) and time of sensation (beginning, middle, and end of session), and duration of the sensation (very short, some minutes, throughout, and after termination of session) end for each session were recorded. The questionnaire was filled before the start of the tDCS intervention and after the last session.

Quality assurance

The measured data were recorded in customized designed forms which were available in print. All the collected data were entered into the specific forms in the Excel (Microsoft Office, 2010). The data entry was double-checked by two independent researchers. After validation of the data by a third researcher, the data were checked for wrong and out-of-range values and any dispute was resolved referring to the print version of the dataset. For the missing data, the missing data point was imputed using linear interpolation to reach the averaged values of the sequential closest values. After the validation, the data were sorted and then entered into statistical package of SPSS (Version 20, Windows) for analyses.