The participants were randomly allocated to 1 of 2 groups. Both groups receive a different nonpharmacological therapy along with a common Ayurvedic formulation for oral consumption. Group 1 received marma therapy for 4 weeks and trayodashanga guggulu for 12 weeks, and group 2 received physiotherapy for 4 weeks along with trayodashanga guggulu for 12 weeks.

Marma therapy is a procedure that includes stimulation of kshipra (point located between the great toe and the second digit of the lower limb), gulpha (point located posterior to the medial malleolus), indrabasti (point located 8 fingerbreadths above the first skin fold of the ankle joint), katikataruna (points located bilaterally along the vertebral column over the hip bone), and janu (point located posterior to the knee joint) marma of the affected limb thrice daily. Out of 108 marma points mentioned in the Ayurvedic texts, these were selected for the said condition, based on the clinical experience of the principal investigator.

Trayodashanga guggulu is a classical multiherb Ayurvedic formulation mentioned in the Ayurvedic Formulary of India, Part-1 [9]. This medicine is procured from a Good Manufacturing Practice–certified pharmacy, and its quality is in compliance with the standards mentioned in the Ayurvedic Pharmacopoeia of India [10].

The mode of delivery, frequency, and duration of each intervention are described below.

For marma therapy, the participants in the trial arm are advised to wear loose and comfortable clothing (without ties, belts, stockings, or such binding clothes) and lie down in the prone or supine position, as per the site to be stimulated. Each of the 5 marma points is stimulated in an upward-to-downward direction in each session. Marma points are stimulated by gentle pressure or vibration using the pulp of the thumb or fingers and the inner side of the knuckle. Each session includes 18 to 20 stimulations to each of the said marma points (1 stimulation lasts for 0.8 seconds). Three such sessions are done each day for 4 weeks. Marma stimulation in female patients is typically performed first in the left extremity, followed by the right extremity, and vice versa in male patients.

For physiotherapy—educational training (eg, advice to avoid sitting for long periods, forward bending, lifting heavy object from ground using leg with knee bending, and trying to tighten the stomach muscles) along with electrotherapy (transcutaneous electrical nerve stimulation with frequency of 20 Hz; pulse width of 100 µs; continuous mode; and 2 channels for 15 minutes, with electrodes placed along the lines of the T12 and S1 vertebrae and intensity increased slowly to a tolerably painful level); hot pack therapy (water at a temperature of 54 °C placed at the lower back for at least 15 minutes, with the patient in hook-lying position); therapeutic exercises suggested based on the case (mostly including drawing-in maneuver, multifidus activation and training, cat-camel exercise, arm lifts and bracing, leg lifts and bracing, single knee-to-chest exercise, and exercises to promote mobility, strength, and range of motion in the lower back); and manual therapy (flexibility training) were provided for 30 minutes per session, 5 sessions per week, for 4 weeks. The participants in the control arm are instructed on the therapeutic exercises and provided with a chart outlining the final positions and necessary instructions.

Trayodashanga guggulu tablets, weighing 500 mg each, are given as oral medication to the study participants in both groups at a dose of 1 g thrice daily, 2 hours after meals, with lukewarm water for 3 months. Participants are allowed to take oral analgesics as rescue medication for pain relief upon telephonic consultation with the investigator. Ongoing medications reported at baseline for any chronic condition (not mentioned in the exclusion criteria) are also continued by the study participants as concomitant medication. Participants who are unwilling to continue, are noncompliant with the study procedure, or meet any exclusion criteria during the study period are withdrawn from the study.

The primary outcome of this study is a reduction in pain intensity in the lumbosacral region and legs (radiating pain) perceived by participants, assessed as the change in the 10 cm VAS score at day 30 and after 3 months from baseline.

The secondary outcomes of this study are improvement in functional disability due to LDH, assessed by the ODI, version 2.0; change in neurodynamic evaluation, assessed using the SLRT; improvement in QoL, assessed by the SF-36; comparison of dependence on allopathic analgesics; and assessment of safety and acceptability of the marma therapy in patients with LDH, assessed by the incidence of adverse events (AEs) associated with the therapy and compliance of patients to marma therapy.

Eligible participants, upon signing the informed consent form, are assessed for screening according to the criteria outlined in the study protocol. Spine examination and neurological assessment by a spine surgeon, systemic examination, SLRT, MRI of the lumbosacral spine, and laboratory investigations (including hemogram, liver function test, renal function test, C-reactive protein, hemoglobin A1c, random blood sugar, rheumatoid factor, and human leukocyte antigen B27 test) are done during the screening of participants before baseline evaluation. Patients undergoing any internal or external therapy or Ayurvedic medication for pain management are instructed to discontinue these treatments, and a baseline evaluation is conducted after a 1-week washout period.

At the baseline visit, general information for personal identification and demographic profiling is collected, medical history is recorded, and a clinical examination for general physical and systemic conditions is done, followed by a detailed neurological examination. Assessment of pain by the 10 cm VAS, functional disability by the ODI, and QoL using the SF-36 is done. The history of consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesic medications during the last 14 days is also noted. The Ayurvedic parameters, such as prakriti, are also assessed at baseline.

The participants are assigned the treatment as per group allocation mentioned on the chit in the opaque sealed envelopes opened by the participant upon baseline evaluation. Each study participant is called daily for the assigned therapy (marma therapy or physiotherapy) for 4 weeks. Oral medication has continued for 12 weeks.

Follow-up and outcome assessments are conducted on days 7, 15, 21, 30, 45, 60, and 90. Any AE reported by a study participant is recorded at each visit and thoroughly assessed for causality. Ongoing events are managed through appropriate interventions, including referral to a higher center when necessary. A telephonic follow-up on day 75 is done to note any AEs, the need for rescue medication, and drug compliance. Details of assessments done during each visit of the study participant are given in Table 1.

A previous study that included physiotherapy as an intervention reported a mean VAS score for back pain of 3.05 (SD 1.36) points after treatment [11]. This was considered to anticipate an improvement of at least 2.79 points after marma therapy. Assuming a between-group difference of 1 point, with 80% power at 5% level of significance, the derived sample size was 72 participants. Furthermore, assuming a 20% attrition rate, the final sample size for this study was 90 participants, randomly allocated to the 2 groups in a 1:1 ratio (n=45, 50% participants per group). The effect size will be determined after the data analysis is completed.

After receiving approval from the Institutional Ethics Committee (IEC) and registering the study with the Clinical Trial Registry of India, all medical and paramedical staff are sensitized to the trial and its eligibility criteria. Patients presenting with concerns related to LBP and associated radiating pain in the lower limb in the OPDs of various departments of the hospital are referred to a special OPD for thorough assessment. Participants are recruited for the study based on the defined inclusion and exclusion criteria. A medical professional and a physiotherapist are delegated the responsibility to screen the patients clinically and get the tests conducted for the patients willing to participate and found to be eligible. Sensitization camps are conducted in nearby areas to create awareness regarding the project at the study site.

The participants are randomized to 2 study groups in the ratio of 1:1. SPSS (version 15.0; IBM Corp) is used to generate the random number sequence. Allocation concealment is ensured by using the sequentially numbered, opaque, sealed envelope technique. The sequence of randomization and preparation of the sealed envelope technique is done centrally by the biostatistics unit at the sponsor’s headquarters. The envelopes are opened by the study participants after completion of the baseline assessment, and the intervention is given to them as per the group allocation. Both the participant and the investigator are aware of the group allocation at the end of the baseline assessment. This trial is an open-label study. However, the research personnel assessing the primary outcome and the secondary outcomes, namely, functional disability and neurodynamic evaluation, were not aware of the group to which participants were allocated.

After screening patients, the eligible participants are included in the study, and data are collected in a case record form (CRF). The data are subsequently recorded as an electronic CRF (e-CRF) on the same day. The CRF is prepared with appropriate coding to be entered into the e-CRF. Periodic data cleaning is performed to ensure the accuracy of the data entered in the e-CRF. The CRFs are stored in a secure location with restricted access.

Before initiating the study, the project team, including the investigators, is trained by the sponsor regarding the study protocol, standard operating procedures for data collection, various assessments, and Good Clinical Practice guidelines. The study participants are informed in detail about the study procedures and follow-up timelines before screening, as well as at the end of the baseline period, before the intervention begins, to confirm their consent for participation in the trial. To minimize loss to follow-up, the study team sends reminder calls and messages to participants 1 to 2 days prior to their scheduled visits.

After verification for accuracy, all collected data will be anonymized prior to statistical analysis. All analyses will follow both the intention-to-treat and per-protocol principles to evaluate the robustness and sensitivity of the results. Any missing or incomplete responses will be addressed through Bayesian imputation. To make the imputation robust, regression-based imputation will also be applied if sufficient information is available in the data. Furthermore, the data will be used for descriptive analysis. Categorical variables will be described as frequencies and percentages, while continuous variables will be summarized as mean (SD) or median (IQR), depending on the distribution of the data (normal or skewed). Inferential analyses will be performed after descriptive analysis of the data. For within-group comparisons, data will be analyzed using the paired 2-tailed t test or the Wilcoxon signed-rank test, depending on the distribution of the data for pre-post observations. Between-group comparisons will be performed using the independent-samples t test or Mann-Whitney U test, depending on the normality of the data.

Repeated-measures ANOVA or the Friedman test will be used for within-group and between-group analyses of the outcomes assessed at multiple time points. The generalized estimating equation and the repeated-measures ANOVA, along with factor analysis, will also be performed if any confounding factors are found during the analysis. Analysis of covariance will be performed if baseline differences between groups are observed. A 2-sided significance level of 5% will be considered for all analyses. All statistical analyses will be performed using Stata software (version 16.1; StataCorp).

A team of technical personnel from the sponsor organization monitors the progress of the trial through regular site visits and data monitoring. The project activities at the study site are supervised to ensure compliance with the standard operating procedures outlined in the protocol and Good Clinical Practice guidelines.

The AEs reported by the study participants on the telephone or during follow-up visits are recorded in a standard format, and adequate details are collected by the study team for investigating causality. Serious AEs will be reported to the IEC and the sponsor within the stipulated timelines.

This research protocol has been reviewed and approved by the IEC of Uttarakhand Ayurved University, Dehradun, Uttarakhand (UAU02/30092021/M1; dated September 30, 2021). The trial is conducted in compliance with the approved protocol and the Declaration of Helsinki.

After thoroughly explaining the study to the patients and giving them the participant information sheet, written consent is obtained before screening. The signature of a witness or a legally authorized representative is obtained in cases where participants are illiterate. One copy of the signed consent form is provided to the study participant, along with the participant information sheet, for their records.

The paper source documents related to the study participants are stored in a place with restricted access, and the computer used for data entry is also password protected. All records that contain names or other personal identifiers, such as locator forms and informed consent forms, are stored separately from study records identified by code numbers. Forms, lists, logbooks, appointment books, and any other listings that link participant ID numbers to other identifying information are stored in a separate, locked file in a restricted area.

The data are analyzed after anonymization. The data will be identified only by coded ID numbers to maintain participant confidentiality. The data will be accessible to the investigators and sponsors. The IEC or any other regulatory body may also be able to access the data after appropriate procedures.

Participants will receive nominal compensation for loss of wages and conveyance costs, with ₹100 (approximately US $1.19) provided for each hospital visit during the study period.

The dissemination of results will be done after the completion of the study and data analysis. The results will be published without disclosing the personal IDs of the participants.

No ancillary studies are proposed for this trial. The participants receive routine Ayurvedic medical care, if required, after completion of the study period.

Deviations from the protocol will not be made except when necessary to alleviate an immediate hazard to trial patients. All protocol amendments, including changes to interventions, examinations, data collection, and methods of analysis, will be reported to the sponsors and the IEC at the earliest opportunity, along with the exact reasons.