Chamomile for Chronic Primary Insomnia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if an herb called chamomile can help to treat insomnia (difficulty in going to sleep or getting enough sleep) by increasing the amount of time that you sleep and/or improving the quality of your sleep. The study will also be looking at the effect of chamomile on day time fatigue and functioning.

Detailed Description
-----------------
Insomnia, defined as the inability to initiate or maintain sleep or lack of restorative sleep, is the most prevalent sleep complaint in primary care. Insomnia is associated with decreased quality of life, work limitations and increased healthcare utilization. Currently there is no treatment for chronic insomnia that is readily available, affordable, without significant side-effects and demonstrated to be safe for long term use. Consequently, treatments that would fill this gap are needed. Chamomile (Matricaria recutita) has been used as a gentle sleep agent by herbalists for several hundred years. It has been studied in animals for its sedative potential and shows promise for treating insomnia. Currently, chamomile's sedative mechanisms of action are unknown, but are thought to be through the major inhibitory neurotransmitter in the central nervous system, γ - aminobutyric acid (GABA). However, no study has examined chamomile's efficacy and safety for treating insomnia. The investigators propose a double-blind, placebo-controlled, randomized trial of chamomile in primary care patients with chronic insomnia. Thirty-four patients will be randomized to either Chamomile High Grade Extract, three 5 mg tablets standardized to 0.4% (-)-α-bisabolol twice daily or placebo and will be followed for 28 days for changes in a sleep diary (sleep efficiency, total sleep time, sleep-onset latency and sleep quality), insomnia severity and sleep disturbances. Secondary endpoints include assessing changes in day time functioning (measures of global quality of life, depression and anxiety) and monitoring for any signs of toxicity. The investigators will also determine the feasibility of conducting a larger trial with this agent.

Official Title
-----------------
A Pilot Grant to Examine the Feasibility, Efficacy and Tolerability of a Standardized Chamomile Extract in Treating Chronic Primary Insomnia

Conditions
-----------------
Primary Insomnia, Chronic Insomnia

Intervention / Treatment
-----------------
* Dietary Supplement: Chamomile High Grade Extract
* Drug: Placebo Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 18 to 64 years; Must be able to give written informed consent; Have a diagnosis of primary insomnia per DSM-IV criteria, reporting < 6.5 hours sleep and/or >30 minutes to fall asleep (SOL) and/or wake after sleep onset (WASO) > 30 minutes, three or more nights per week; Present sleep complaint for at least 6 months; Exclusion Criteria: Women who are pregnant, lactating or less than six months post-partum. Due to the fact that an assessment of reproductive performance and teratology tests have not been conducted we are excluding pregnant and lactating women; Patients with unstable medical conditions; DSM-IV Axis I or personality disorder diagnosis with the exception of patients with treated and stable unipolar depression or generalized anxiety disorder (such that the PRIME-MD scores are within normal range for these disorders); Difficulty in sleep initiation or maintenance associated with known medical diagnosis or conditions that may affect sleep, e.g., sleep apnea, restless leg syndrome, chronic pain; Evidence of lack of reliability or noncompliance as defined by missing a pretreatment appointment more than twice; Current diagnosis of substance abuse or dependence; Known allergy to chamomile or members of the ragweed family; Currently taking cyclosporine, warfarin or chronic sedative and anxiolytic medications; Prior use of insomnia medications is not exclusionary, but patients must be off of these medications at the screening visit and through out the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chamomile High Grade Extract<br>Each capsule contains 90 mg dry extract of chamomile flowering tops [6:1 (v/v) extraction solvent (ethanol 70%/30% water): flowering tops] standardized up to 2.5 mg of (-)-α-bisabolol and ≥ 2.5 mg of apigenin per tablet | Dietary Supplement: Chamomile High Grade Extract<br>* three tablets each (equivalent to 7.5 g of dried herb) p.o. twice daily for 28 days<br>|
| Placebo Comparator: Placebo Tablet<br>Contained lactose | Drug: Placebo Tablet<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Chamomile Extract on Measures of Sleep at Day 28. | Change from baseline of chamomile extract, three tablets (equivalent to 7.5 g of dried herb) p.o. twice times daily versus placebo on the following sleep measures at 28 days: the change from baseline of daily self-report of sleep as assessed by a sleep diary that includes determination of: (i) sleep efficiency, which equals The total sleep time divided by time-in-bed, multiplied by 100. This measure is our primary aim (SE). | baseline and day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Chamomile on Daytime Functioning Measures: BDI | Change from baseline of chamomile extract, three tablets p.o. twice times daily versus placebo on daytime functioning measures at 28 days: the change from baseline of measures of depression and anxiety evaluated respectively with the Beck Depression Inventory-II (BDI-II), which is scored on a scale of 0 to 63 where a total score of 0-13 is considered minimal range (minimal depression), 14-19 is mild, 20-28 is moderate, and 29-63 is severe. | baseline and day 28 | 
| Change From Baseline of Chamomile on Daytime Functioning Measures: STAI | Change From Baseline of Chamomile on Daytime Functioning Measures, depression and anxiety evaluated respectively with the Beck Depression Inventory-II (BDI-II) and trait portrait of the State Trait Anxiety Index (STAI). STAI scores range for each subtest from 20-80, the higher score indicating greater anxiety. A cut point of 39-40 has been suggested to detect clinically significant symptoms for the S-Anxiety scale | Baseline and 28 days | 
| Change From Baseline of Chamomile on Daytime Functioning Measures: Fatigue Severity Scale | Change From Baseline of Chamomile on Daytime Functioning Measures: Fatigue Severity Scale (FSS) Range: 9 to 63. The 9-item scale measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity. | Baseline and 28 days | 
| Change From Baseline of Chamomile on Daytime Functioning Measures [ Time Frame: Baseline and Day 28 ] | the change from baseline of global QOL (as determined by the 12 Item Short Form Health Survey Version 2 {SF-12 V2}) | Baseline and 28 days | 
| Changes From Baseline in the Safety and Tolerability of Chamomile | Changes from baseline in the safety and tolerability of Chamomile High Grade Extract, three tablets (equivalent to 7.5g of dried herb) p.o. twice times daily versus placebo were measured by counting all participants who reported a serious or non-serious adverse event at the weekly check-ins that were established. | once per week during study and day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Matricaria, Chamomile, Herb, Insomnia