Generalized Anxiety DisorderPhase 3NCT01072344
Long Term Chamomile Therapy for Anxiety
A Phase 3 study testing Chamomile (Matricaria recutita) in people with Generalized Anxiety Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
Prior research has shown that chamomile may be an effective, short-term anti-anxiety treatment. This study will examine the initial and long-term benefits of chamomile extract therapy for the prevention of recurrent anxiety disorder. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Generalized Anxiety Disorder
- What is being tested?
- Chamomile (Matricaria recutita)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to Jun 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women at least 18 years old (all races and ethnicity)
- DSM IV diagnosis of GAD as the primary anxiety disorder
- Baseline GAD-7 score ≥ 10
- Baseline CGI/S score at least 4
- Not taking anti-anxiety medication (e.g., Benzodiazepines, buspirone, antidepressants)
- Not taking antidepressant, mood stabilizer, or tranquilizer therapy for a prior DSM IV Axis I mood disorder that is in remission
- Able to understand and provide informed consent
- Able to participate in a 38-week study
Who cannot join
- Patients < 18 years old
- Primary DSM IV Axis I anxiety disorder other than GAD (e.g., panic disorder with or without agoraphobia, phobia disorder, acute stress disorder, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, substance-induced anxiety disorder)
- Current DSM IV Axis I psychotic disorder
- Substance abuse or dependence within the prior 3 months
- Current DSM IV Axis I bipolar or major depressive disorder [Note: Patients with co-morbid depressive disorder NOS (e.g., minor depression, recurrent brief depressive disorder, or premenstrual dysphoric disorder (PMDD)] will not be excluded
- Unstable medical condition
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- Allergy to chamomile
- Documented allergy to plants of the asteraceae family (e.g., ragweed, asters, chrysanthemum)
- Allergic to mugwort or birch pollen
- Concurrent anti-anxiety tranquilizer, antidepressant or mood stabilizer therapy
- Concurrent use of over-the-counter anti-anxiety and/or antidepressant preparations (e.g., chamomile, St. John's Wort, kava kava)
- Concurrent use of established antidepressant, mood stabilizer, or tranquilizer therapy for pre-existing affective disorder. [Note: Patients with a history of affective disorder (in remission) who are not currently taking antidepressant, mood stabilizer, or tranquilizer therapy are not excluded from the trial]
- Women of child-bearing potential not willing to use a medically proven form of contraception
- Positive pregnancy test
- Actively suicidal or suicide attempt within the preceding 12 months
Trial locations and contacts
1 site in 1 country.
United States1 site
Depression Research Unit
Philadelphia, Pennsylvania, 19104-3309
About this study
Official title: Long-Term Chamomile Therapy for Generalized Anxiety Disorder (GAD)
Prior research has shown that chamomile may be an effective, short-term anti-anxiety treatment. This study will examine the initial and long-term benefits of chamomile extract therapy for the prevention of recurrent anxiety disorder.
Read the detailed description
Anxiety disorders are among the most common psychiatric conditions. They affect up to 25% of the US adult population. Generalized anxiety disorder (GAD) is a chronic, recurrent form of the disorder. Although benzodiazepines and serotonin reuptake inhibitors have become the mainstay therapy of GAD, these drugs are often associated with unwanted side effects, habituation, and withdrawal symptoms. Many individuals decline using conventional drug therapy for financial, cultural, or personal reasons such as the stigma of mental illness. As a result, many individuals will seek alternative therapy for their anxiety symptoms. The identification of effective alternative therapies for GAD would be of particular relevance. Among alternative therapies for anxiety, chamomile has been used as a traditional herbal medicine for its calming effect. It is well tolerated and demonstrates pharmacological activity in animal models of anxiety. Despite its widespread use and availability, there has been only one clinical trial of chamomile safety and efficacy in GAD. The current application seeks to build upon the results of that prior chamomile study. In that 8-week, double-blind, placebo-controlled trial, we found a significant superiority of chamomile (vs. placebo) in reducing GAD symptoms. We also found chamomile to be exceedingly well tolerated (vs. placebo). The current application seeks to extend these promising preliminary results by conducting a randomized, double-blind, parallel group, placebo-substitution, long-term safety and efficacy study of chamomile in preventing GAD relapse. For specific aim #1 we will ask: "Does long-term chamomile therapy (vs. placebo) prolong the time to relapse of anxiety symptoms following recovery from GAD?" To answer this question, 180 patients with moderate to severe GAD will receive open-label chamomile extract 500-1,500 mg daily for 8 weeks. Responders to chamomile, who remain well for 4 additional weeks of consolidation therapy, will be randomized to double-blind continuation therapy with chamomile 500-1,500 mg daily or placebo for an additional 26 weeks. We hypothesize that continuation chamomile therapy will result in a prolonged time to relapse (vs. placebo). For specific aim #2 we will ask: "What is the relative safety and tolerability of long-term chamomile therapy (vs. placebo) in patients who have recovered from GAD?" To answer this question, we will examine the following outcome measures: (i) the proportion of patients in each treatment condition who relapse; (ii) the frequency, severity, and duration of treatment-emergent adverse events; (iii) the frequency of discontinuation symptoms during initial double-blind therapy; and, (iv) the frequency of early study discontinuation. We hypothesize that chamomile therapy will result in a lower proportion of anxiety relapses and a lower study discontinuation rate (vs. placebo). We further hypothesize that chamomile therapy will result in a similar frequency of discontinuation symptoms and treatment-emergent adverse events (vs. placebo).
- Conditions
- Generalized Anxiety Disorder
- Being tested
- Chamomile (Matricaria recutita)
- Keywords
- Anxiety, Chamomile, Herbal Remedy, Complementary and Alternative Medicine
- Medical subject headings
- Generalized Anxiety Disorder, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chamomile (Matricaria recutita)Drug
Also called Chamomile
500 mg 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Chamomile Extract | Experimental | Pharmaceutical grade oral chamomile extract. Receives: Drug: Chamomile (Matricaria recutita) |
| Placebo | Placebo comparator | Pharmaceutical grade lactose monohydrate. Receives: Drug: Chamomile (Matricaria recutita) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Relapse in Each Treatment Condition.
The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Relapse is dichotomously defined as an increase in CGI/S (a clinician-rated global measure of anxiety's severity) score from ≤ 3 (at study visit 6) to ≥ 4 (on two consecutive scheduled or unscheduled study visits ≥ 2 weeks apart) plus meeting DSM IV-TR criteria for GAD (minus the 6-month time criterion).
Measured: 26 weeks
Secondary outcomes (4)
The Proportion of Subjects in Each Treatment Condition Who Relapse.
The proportion of subjects in each treatment condition who relapsed after randomization
Measured: 26 weeks
Frequency, Severity, and Duration of Treatment-emergent Adverse Events.
We will report the frequency, severity, and duration of treatment-emergent adverse events by treatment arm.
Measured: 26 weeks
Frequency of Discontinuation Symptoms at the Start of Double-blind Therapy in Each Treatment Condition.
Discontinuation emergent signs and symptoms checklist (DESS) is a patient-rated measure of the presence and severity of discontinuation symptoms occurring after medication discontinuation. %
Measured: 26 weeks
Frequency of Early Study Discontinuation in Each Treatment Condition.
This is the # of subjects who discontinued the study during randomization phase due to other reasons.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Generalized Anxiety DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jun J Mao, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01072344
- Sponsor's protocol ID
- AT005074
- Status last verified
- Jun 2017
- First submitted
- 18 Feb 2010
- Last updated
- 6 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Keefe JR, Guo W, Li QS, Amsterdam JD, Mao JJ. An exploratory study of salivary cortisol changes during chamomile extract therapy of moderate to severe generalized anxiety disorder. J Psychiatr Res. 2018 Jan;96:189-195. doi: 10.1016/j.jpsychires.2017.10.011. Epub 2017 Oct 16.
PubMed 29080520Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine. 2016 Dec 15;23(14):1735-1742. doi: 10.1016/j.phymed.2016.10.012. Epub 2016 Oct 24.
PubMed 27912875Keefe JR, Amsterdam J, Li QS, Soeller I, DeRubeis R, Mao JJ. Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder. J Psychiatr Res. 2017 Jan;84:90-97. doi: 10.1016/j.jpsychires.2016.09.029. Epub 2016 Sep 30.
PubMed 27716513
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Chamomile Therapy for Generalized Anxiety Disorder (GAD)
- ClinicalTrials.gov ID
- NCT01072344
- Acronym / sponsor ID
- AT005074
- Conditions
- Generalized Anxiety Disorder
- Keywords
- Anxiety, Chamomile, Herbal Remedy, Complementary and Alternative Medicine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 22 Feb 2010 (estimated)
- Results
- Posted 6 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prior research has shown that chamomile may be an effective, short-term anti-anxiety treatment. This study will examine the initial and long-term benefits of chamomile extract therapy for the prevention of recurrent anxiety disorder.
Detailed description
Anxiety disorders are among the most common psychiatric conditions. They affect up to 25% of the US adult population. Generalized anxiety disorder (GAD) is a chronic, recurrent form of the disorder. Although benzodiazepines and serotonin reuptake inhibitors have become the mainstay therapy of GAD, these drugs are often associated with unwanted side effects, habituation, and withdrawal symptoms. Many individuals decline using conventional drug therapy for financial, cultural, or personal reasons such as the stigma of mental illness. As a result, many individuals will seek alternative therapy for their anxiety symptoms. The identification of effective alternative therapies for GAD would be of particular relevance. Among alternative therapies for anxiety, chamomile has been used as a traditional herbal medicine for its calming effect. It is well tolerated and demonstrates pharmacological activity in animal models of anxiety. Despite its widespread use and availability, there has been only one clinical trial of chamomile safety and efficacy in GAD. The current application seeks to build upon the results of that prior chamomile study. In that 8-week, double-blind, placebo-controlled trial, we found a significant superiority of chamomile (vs. placebo) in reducing GAD symptoms. We also found chamomile to be exceedingly well tolerated (vs. placebo). The current application seeks to extend these promising preliminary results by conducting a randomized, double-blind, parallel group, placebo-substitution, long-term safety and efficacy study of chamomile in preventing GAD relapse. For specific aim #1 we will ask: "Does long-term chamomile therapy (vs. placebo) prolong the time to relapse of anxiety symptoms following recovery from GAD?" To answer this question, 180 patients with moderate to severe GAD will receive open-label chamomile extract 500-1,500 mg daily for 8 weeks. Responders to chamomile, who remain well for 4 additional weeks of consolidation therapy, will be randomized to double-blind continuation therapy with chamomile 500-1,500 mg daily or placebo for an additional 26 weeks. We hypothesize that continuation chamomile therapy will result in a prolonged time to relapse (vs. placebo). For specific aim #2 we will ask: "What is the relative safety and tolerability of long-term chamomile therapy (vs. placebo) in patients who have recovered from GAD?" To answer this question, we will examine the following outcome measures: (i) the proportion of patients in each treatment condition who relapse; (ii) the frequency, severity, and duration of treatment-emergent adverse events; (iii) the frequency of discontinuation symptoms during initial double-blind therapy; and, (iv) the frequency of early study discontinuation. We hypothesize that chamomile therapy will result in a lower proportion of anxiety relapses and a lower study discontinuation rate (vs. placebo). We further hypothesize that chamomile therapy will result in a similar frequency of discontinuation symptoms and treatment-emergent adverse events (vs. placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chamomile Extract | Experimental | Drug: Chamomile (Matricaria recutita)Pharmaceutical grade oral chamomile extract. |
| Placebo | Placebo comparator | Drug: Chamomile (Matricaria recutita)Pharmaceutical grade lactose monohydrate. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men and women at least 18 years old (all races and ethnicity)
- DSM IV diagnosis of GAD as the primary anxiety disorder
- Baseline GAD-7 score ≥ 10
- Baseline CGI/S score at least 4
- Not taking anti-anxiety medication (e.g., Benzodiazepines, buspirone, antidepressants)
Key exclusion criteria (15 listed)
- Patients < 18 years old
- Primary DSM IV Axis I anxiety disorder other than GAD (e.g., panic disorder with or without agoraphobia, phobia disorder, acute stress disorder, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, substance-induced anxiety disorder)
- Current DSM IV Axis I psychotic disorder
- Substance abuse or dependence within the prior 3 months
- Current DSM IV Axis I bipolar or major depressive disorder [Note: Patients with co-morbid depressive disorder NOS (e.g., minor depression, recurrent brief depressive disorder, or premenstrual dysphoric disorder (PMDD)] will not be excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chamomile (Matricaria recutita)Also: Chamomile500 mg 3 times daily | Drug | Chamomile Extract, Placebo |
Primary outcome
Time to Relapse in Each Treatment Condition.
Time frame: 26 weeks
The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Relapse is dichotomously defined as an increase in CGI/S (a clinician-rated global measure of anxiety's severity) score from ≤ 3 (at study visit 6) to ≥ 4 (on two consecutive scheduled or unscheduled study visits ≥ 2 weeks apart) plus meeting DSM IV-TR criteria for GAD (minus the 6-month time criterion).
4 secondary outcomes
The Proportion of Subjects in Each Treatment Condition Who Relapse.
Time frame: 26 weeks
Frequency, Severity, and Duration of Treatment-emergent Adverse Events.
Time frame: 26 weeks
Frequency of Discontinuation Symptoms at the Start of Double-blind Therapy in Each Treatment Condition.
Time frame: 26 weeks
Frequency of Early Study Discontinuation in Each Treatment Condition.
Time frame: 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29080520Keefe JR, Guo W, Li QS, Amsterdam JD, Mao JJ. An exploratory study of salivary cortisol changes during chamomile extract therapy of moderate to severe generalized anxiety disorder. J Psychiatr Res. 2018 Jan;96:189-195. doi: 10.1016/j.jpsychires.2017.10.011. Epub 2017 Oct 16.
- Derived from this study: PubMed 27912875Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine. 2016 Dec 15;23(14):1735-1742. doi: 10.1016/j.phymed.2016.10.012. Epub 2016 Oct 24.
- Derived from this study: PubMed 27716513Keefe JR, Amsterdam J, Li QS, Soeller I, DeRubeis R, Mao JJ. Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder. J Psychiatr Res. 2017 Jan;84:90-97. doi: 10.1016/j.jpsychires.2016.09.029. Epub 2016 Sep 30.
- University of Pennsylvania Depression Research Unit WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jun J Mao, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chamomile (Matricaria recutita) in people with Generalized Anxiety Disorder, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Relapse in Each Treatment Condition. (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01072344, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2017.