Chamomile for Chronic Primary Insomnia

• ClinicalTrials.gov Identifier: NCT01286324
• Recruitment Status: Completed
• First Posted: January 31, 2011
• Results First Posted: July 30, 2013
• Last Update Posted: November 7, 2017
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Suzanna Zick, University of Michigan

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Primary Insomnia; Chronic Insomnia	Dietary Supplement: Chamomile High Grade Extract; Drug: Placebo Tablet	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Grant to Examine the Feasibility, Efficacy and Tolerability of a Standardized Chamomile Extract in Treating Chronic Primary Insomnia
• Study Start Date: July 2008
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Chamomile High Grade Extract; 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; three tablets each (equivalent to 7.5 g of dried herb) p.o. twice daily for 28 days
Placebo Comparator: Placebo Tablet; Contained lactose	Drug: Placebo Tablet

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline of Chamomile Extract on Measures of Sleep at Day 28. [ Time Frame: baseline and 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).

Secondary Outcome Measures :

1. Change From Baseline of Chamomile on Daytime Functioning Measures: BDI [ Time Frame: baseline and day 28 ]

   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.
2. Change From Baseline of Chamomile on Daytime Functioning Measures: STAI [ Time Frame: Baseline and 28 days ]
   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
3. Change From Baseline of Chamomile on Daytime Functioning Measures: Fatigue Severity Scale [ Time Frame: Baseline and 28 days ]

   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.

4. Change From Baseline of Chamomile on Daytime Functioning Measures [ Time Frame: Baseline and Day 28 ] [ Time Frame: Baseline and 28 days ]
   the change from baseline of global QOL (as determined by the 12 Item Short Form Health Survey Version 2 {SF-12 V2})
5. Changes From Baseline in the Safety and Tolerability of Chamomile [ Time Frame: once per week during study and day 28 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Michigan

University of Michigan Department of Family Medicine

Ann Arbor, Michigan, United States, 48105

Sponsors and Collaborators

University of Michigan

Investigators

• Principal Investigator: Suzanna M Zick, ND, MPH; University of Michigan
• Study Director: J. Todd Arnedt, PhD; University of Michigan

More Information

Publications of Results:

Zick SM, Wright BD, Sen A, Arnedt JT. Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study. BMC Complement Altern Med. 2011 Sep 22;11:78. doi: 10.1186/1472-6882-11-78.

• Responsible Party: Suzanna Zick, Research Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT01286324
• Other Study ID Numbers: 101,749
• First Posted: January 31, 2011
• Results First Posted: July 30, 2013
• Last Update Posted: November 7, 2017
• Last Verified: October 2017

Keywords provided by Suzanna Zick, University of Michigan:

Matricaria; Chamomile; Herb; Insomnia

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders