A Study Protocol for Randomized Waitlist-Controlled Trial on the Efficacy of Shirolepa in Adults with Primary Insomnia

Abstract

Background and Objectives:

Adults aged 18–60 years are recommended to have a sound sleep of 7 or more hours per night. Lack of sleep due to sleep disturbances, such as insomnia, causes significant impairment in an individual's quality of life. Insomnia shares many similarities with the condition mentioned in Ayurveda as nidranasha. The general Ayurvedic approach to insomnia includes a combination of therapies and internal medications. Ayurvedic therapies such as shirodhara (oil-dripping therapy), takradhara (buttermilk-dripping therapy), shirobasti (retention of oil on the head), and shirolepa (application of medicated paste over the head) are commonly used in the treatment of insomnia. However, no studies have been conducted to evaluate the role of shirolepa although it is widely practiced by Ayurvedic practitioners. Therefore, this study aims to evaluate the effect of shirolepa in adults with primary insomnia using subjective and objective parameters.

Design:

Two group pretest post-test design with randomization and waitlist control with 1:1 allocation ratio.

Methods:

The protocol adheres to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Thirty-eight adults aged between 18 and 60 years with primary insomnia will be randomly assigned to intervention and waitlist control groups in 1:1 allocation ratio. The intervention group will receive shirolepa (application of medicinal herbal paste on the head) for 7 consecutive days. The control group will receive shirolepa after the post-test assessment. Our primary outcome is insomnia severity, which is evaluated using the Insomnia Severity Index. Secondary outcome measures will be evaluated using Pittsburgh Sleep Quality Index, Sleep Diary, Epworth Sleepiness Scale, and wrist actigraphy.

Ethics and Dissemination:

Ethical clearance was obtained from the Institutional Ethics Committee (01/PK/IEC/2021), and the trial was registered in the Clinical Trials Registry of India (CTRI/2022/09/045226). The study results will be reported and published in peer-reviewed journals.

Administrative Information

Administrative information of the trial as per Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines is detailed in Table 1.

Table 1.

Administrative Information of the Trial

Title	A Study Protocol for Randomized Waitlist-Controlled Trial on the Efficacy of Shirolepa in Adults with Primary Insomnia
Trial registration	CTRI/2022/09/045226
Protocol version	August 5, 2021 (Version 1)
Funding	No funding sources available.
Roles and responsibilities	LA conceived of this study and wrote the original draft of the protocol. RV and SS reviewed it. RV is the project administrator and manages resources. SS supervises the trial. All authors contributed to refinement of the study protocol and approved the final article.

LA, Lochan Acharya; RV, Remya Vijayan; SS, Seena S.

Introduction

Background and rationale

The recommended hours of sleep per night for adults between the ages of 18 and 60 years is 7 or more hours. ¹ Lack of sleep due to sleep disturbances, such as insomnia, causes significant impairment in an individual's quality of life.

Insomnia is one of the most common forms of sleep disturbance, with a prevalence of 18–33% in India.^2–4 Almost 15% of insomnia patients suffer from daytime consequences such as fatigue and malaise, memory and concentration difficulties, mood disturbances and irritability, and behavioral problems such as hyperactivity and aggression.^5,6 Currently, the mainstay treatment for insomnia is a behavioral approach and psychological treatment complemented with medications.

Tranquilizers and sedatives, such as benzodiazepines and barbiturates, are the first-line pharmacological treatment for primary insomnia; however, there are concerns about residual symptoms, such as excessive sedation, tolerance, addiction, and neurological toxicity after longer usage. ⁷ The overall management of insomnia seems to be unsatisfactory in the conventional system of medicine, as health surveys also show that ∼1.6 million adults with insomnia in the United States opt for complementary and alternative therapies annually. ⁸ Therefore, there is a growing need to evaluate the role of alternative therapies in the management of insomnia.

Ayurveda has placed significant importance on sleep and considers sleep as one of the three sub-pillars of health. ⁹ It mentions that an individual can achieve happiness, nourishment, physical and mental strength, virility, knowledge, and longevity through sound and timely sleep, which signifies sleep as an important indicator of both physical and mental well-being. ¹⁰

Insomnia shares many similarities with the condition mentioned in Ayurveda as nidranasha. According to Ayurveda, lack of sleep leads to various types of physical and mental symptoms. ¹¹ Caraka Samhita, a classical Ayurvedic book, has mentioned frequent yawning, body pain, stupor, headache, and heavy eyes as consequences of lack of sleep. ¹² These are usually the symptoms associated with insomnia.

According to Ayurveda, the vitiation of vata and pitta dosha causes insomnia. The general principle of the management of insomnia in Ayurveda is to bring the involved Dosha into normalcy. Ayurveda has a holistic insomnia approach with a concoction of therapies and internal medications. ¹³ The general approach to insomnia includes a combination of therapies and internal medications. Ayurveda therapies such as shirodhara (oil-dripping therapy), ¹⁴ takradhara (buttermilk-dripping therapy), ¹⁵ shirobasti (retention of oil on the head), ¹⁶ and shirolepa (application of medicinal herbal paste on the head) ¹⁷ are also commonly used in the treatment of insomnia. The benefits of such external therapies are that they are noninvasive and are thought to be economical and less time consuming.

Very few studies have explored the stand-alone effect of Ayurvedic therapies on primary insomnia. Some studies have been conducted to evaluate the role of shirodhara in mitigating the symptoms of primary insomnia.^14,18 However, to date, no studies have been conducted to evaluate the role of shirolepa although it is widely practiced by Ayurvedic practitioners. Similarly, one major limitation of existing studies that evaluate the role of any Ayurvedic intervention in insomnia is that they lack objective evaluation and depend on subjective evaluation, which tends to report bias.^19,20 Therefore, this study aims to evaluate the effect of shirolepa in adults with primary insomnia using subjective and objective parameters.

Objectives

The primary objective of the study is to evaluate whether shirolepa improves the severity of insomnia in adults with primary insomnia compared with the waitlist control. The secondary objectives of the trial are to evaluate whether shirolepa improves the sleep quality and severity of daytime consequences.

Trial design

The protocol adheres to SPIRIT guidelines. ²¹ Two group pretest post-test design with randomization and waitlist control with 1:1 allocation ratio will be used in this study. Figure 1 illustrates the proposed trial design.

FIG. 1.

Flowchart displays the overall trial study design.

We have preferred a waitlist control as it provides a noninterventional comparator to the study. ²² As a waitlist control, participants can still receive treatment after a short period of withholding without any negative changes in their baseline clinical characteristics. ²³

Materials and Methods

Study setting

This research study will be conducted at the Government Ayurveda College, Tripunithura, Kerala, India.

Eligibility criteria

We will recruit participants aged 18–60 years of any gender diagnosed with primary insomnia as per the Research Diagnostic Criteria for primary insomnia. ²⁴ Participants will be screened based on the Insomnia Severity Index (ISI) and only those with mild to moderate insomnia will be recruited. ²⁵ Similarly, those with moderate to severe depressive or anxiety symptoms, and higher levels of stress on the depression anxiety stress scale-21 scale, will be excluded from the study. ²⁶ Complete list of inclusion and exclusion criteria for the trial participants are presented in Table 2.

Table 2.

Eligibility Criteria for the Study

Inclusion criteria	Exclusion criteria
1. Between the age group 18 and 60, irrespective of gender 2. Diagnosed with primary insomnia as per research diagnostic criteria for primary insomnia 25 3. ISI score of more than 8 but less than 21 points (mild to moderate insomnia) 4. Willing to participate and able to consent	1. Indication of moderate/severe depressive or anxiety symptoms (score ≥14 on the depression scale, score ≥10 on the anxiety scale and score ≥19 on the stress scale of DASS-21) 26 2. Undergoing treatment or had taken any treatment for insomnia in <3 months 3. Pregnant or lactating women 4. Nocturnal shiftwork (i.e., working between 12:00 am and 6:00 am)

DASS-21, depression anxiety stress scale-21; ISI, insomnia severity index.

Intervention

Shirolepa is a noninvasive Ayurvedic therapy in which medicinal herbal paste is applied on the head and covered with some leaf for a specified time duration. Participants in the intervention group will undergo shirolepa therapy once a day at the study site for 7 consecutive days, from 4:00 pm to 5:00 pm. The liquid medium for the paste is medicated takra (buttermilk), which is prepared according to the traditional method of preparation practiced in Kerala, India. To this, the Panchagandha churna (a classical Ayurvedic powder) will be mixed, and the paste will be made. The paste will be applied directly on the scalp without removing the hair.

Trained Ayurveda therapists or resident doctors will do the therapy within the study facility. Participants in the waitlist control group will receive the same intervention after completing post-test assessments.

The standard operating procedure (SOP) for the study intervention was adopted from the manual prepared by the Department of Panchakarma, Government Ayurveda College, Tripunithura, for the Panchakarma Pre-Workshop in connection with the Global Ayurveda Festival, 2014. ²⁷ The SOP is explained in the Supplementary Data. ²⁸

Outcome measures

Primary outcome measures

1. 1.

   ISI: ²⁵ ISI is a seven-item measure of the nature, severity, and effects of insomnia. Based on a 5-point Likert type scale (0 = no problem; 4 = severe problem), the scores ranged from 0 to 28. The scoring interpretation is as follows: 0–7 = no clinically significant insomnia, 8–14 = subclinical insomnia, 15–21 = clinical insomnia, 22–28 = severe clinical insomnia.

Secondary outcome measures

1. 1.

   Pittsburgh Sleep Quality Index (PSQI): ²⁹ PSQI provides a subjective measure of sleep quality and patterns. It contains 19 self-rated questions and five questions rated by the bed partner or roommate (if one is available). There are seven component scores from 0 to 3 to points that are then added to yield one global score with a range from 0 to 21 points. A score >5 indicates poor sleep quality.

2. 2.

   Sleep parameters of the actigraphy wristwatch: ³⁰ Actigraphy provides objective estimates of sleep parameters, including Sleep Latency, Wake After Sleep Onset (WASO), no nighttime awakening, sleep efficiency (SE), sleep awakening, and total sleep time (TST). Actigraphy assessment will be performed for a minimum of 3 consecutive days at every assessment point, and the mean of the measurements will be taken for analysis. ³¹ Participants will be asked to wear the actigraphy wristwatch on the nondominant wrist during the evaluation period. A previously validated actigraphy wristwatch will be used in the study.

3. 3.

   Sleep diary: ³² The sleep diary provides subjective estimates of daily sleep parameters, including sleep onset latency, WASO, number of awakenings, SE, TST, and subjective feelings of rest. Participants will be asked to fill out the sleep diary within 30 min of awakening in the morning. Participants will be asked to complete the sleep diary for at least 7 consecutive days before and after the intervention, and the mean of the measurements will be taken for analysis.

4. 4.

   Epworth Sleepiness Scale (ESS): ³³ ESS contains eight items that require self-reported disclosure of the expectation of “dozing” in a variety of situations. The sum of responses is calculated for a total score that ranges from 0 to 24. Higher scores indicate a worse outcome.

Participant timeline

See Table 3.

Table 3.

Participation Timeline

	Study period
			Postallocation		Close-out
	Enrolment	Allocation	Pretest	Intervention	Post-test
Time points	0	0	1 week	1 week	1 week
Enrolment
Eligibility screening	X
Informed consent	X
Allocation		X
Interventions
Shirolepa or waitlist				X
Assessments
Sleep diary			X		X
ISI	X		X		X
PSQI			X		X
ESS			X		X
Actigraphy			X		X

ESS, Epworth Sleepiness Scale; PSQI, Pittsburgh Sleep Quality Index.

Sample size

Sample size is calculated based on the previous study. ²⁵ In that study, the mean change in the ISI before and after treatment was 4 (d = 4) and the standard deviation of the values was 4.2 (σ = 4.2). Based on a two-tailed alpha error of 5% and with a statistical power of 80%, the calculated sample size is based on the following equation: ³⁴ $$N=C\times \frac{2{\sigma }^2}{d^2}=7.84\times \frac{2\times {4.2}^2}{4^2}=17.2872,$$

where C is the constant for the 95% confidence interval and 80% power. Assuming a 10% dropout and a random assignment of participants between the intervention and waitlist control groups in a 1:1 ratio, the total sample size is of 38.

Recruitment

Participants will be recruited from the outpatient department of the Government Ayurveda College, Tripunithura, where they will be approached by the study team or can respond to advertisements posted on the hospital's notice board.

Randomization and blinding

Randomization

Participants will be block-randomized into the Intervention Group and Waitlist Control Group in a 1:1 ratio. Four blocks of size 6 (4 × 6) and four blocks of size 4 (4 × 4) were made using a web-based generator called Sealed Envelope. ³⁵

Blinding

Randomization will be done by a faculty member who is independent of the study team and will be blinded to the study participants. Both the principal investigator and the participants will not be blinded to treatment group due to the nature of the intervention. The principal investigator and outcome assessors are different individuals in this study. Participants will be asked not to disclose their treatment to ensure blinding of the outcome assessor. Outcome assessors and statisticians will be blinded to group assignment and participant characteristics.

Data collection, management, and analysis

Data collection methods

Demographic and socioeconomic data will be taken at the time of the screening. Clinical proforma will be used to record all the aspects of the participants, including ashtavidha and dashavidha pariksha (Ayurvedic methods of patient examination). A validated questionnaire will be used to identify the prakriti (body constituent according to Ayurveda) of the participants before the intervention. ³⁶ Data for the outcome measures will be collected using validated questionnaires (viz. ISI, PSQI, and ESS) and actigraphy wristwatch before and after the intervention.

Data management

All data will be stored securely and separately in department folders. Only the principal investigator and study supervisors will have access to the folders.

Statistical methods

Based on the distribution of data, appropriate statistical test will be used. For before–after changes in outcome variables in each group (within group), a paired t-test or Wilcoxon signed-rank test will be conducted. To compare the effect of the intervention between the two groups, an independent sample t-test or Mann–Whitney U test will be conducted. A chi-square test will be used to assess prakriti (body constitution) differences among groups based on a validated scale. The significance level will be set at p < 0.05 where appropriate.

Ethics and Dissemination

Research ethics approval

Ethical clearance was obtained from the Institutional Ethics Committee (01/PK/IEC/2021) and the trial was registered in the Clinical Trials Registry of India (Registration: CTRI/2022/09/045226). Trial will be performed according to the latest version of the Declaration of Helsinki. Written informed consent will be obtained from all participants before enrolment.

Protocol amendments

The protocol has not been amended after ethical approval.

Consent

Informed consent will be fully obtained from all patients before the trial, and the autonomy of the patient will be given utmost respect.

Confidentiality

All participant-related information will be held confidential throughout all phases of the study and stored securely in the department. Only the principal investigator will have access to the storage.

Access to data

The principal investigator and study coordinator will have access to the data and, if needed, will be shared adhering to the guidelines of the International Committee of Medical Journal Editors after the study is completed.

Dissemination policy

The study results will be reported and published in peer-reviewed journals.

Discussion

This study will be the first to evaluate the stand-alone efficacy of Ayurvedic therapy in primary insomnia using both subjective and objective parameters. Currently, no data are available on the effect of shirolepa therapy in the treatment of primary insomnia. The study is designed to address this gap in the literature. However, there are some limitations in the study. We were not able to double-blind the study due to the nature of the intervention. A follow-up evaluation will not be carried out in the study, so we cannot estimate how long the therapeutic effect will remain.