A Phase 3 interventional study of Chamomile (Matricaria recutita) in Generalized Anxiety Disorder, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2017-07-06.
Sponsored by University of Pennsylvania · Phase 3, Interventional, and Treatment
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.
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).
4,868 studies on the registry are indexed under Anxiety Disorders; 1,390 are open to participants now.
This study's enrollment of 180 is above the median of 80 across 4,174 interventional studies indexed under Anxiety Disorders.
Browse Anxiety Disorders studies →University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.
Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.
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Exclusion Criteria:
Pharmaceutical grade oral chamomile extract.
Drug: Chamomile (Matricaria recutita)
Pharmaceutical grade lactose monohydrate.
Drug: Chamomile (Matricaria recutita)
500 mg 3 times daily
Also known as: Chamomile
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).
Time frame: 26 weeks
The Proportion of Subjects in Each Treatment Condition Who Relapse.
The proportion of subjects in each treatment condition who relapsed after randomization
Time frame: 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.
Time frame: 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. %
Time frame: 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.
Time frame: 26 weeks
| Milestone | Chamomile Extract | Placebo |
|---|---|---|
| Started | 46 | 47 |
| Completed | 35 | 29 |
| Not completed | 11 | 18 |
| Withdrew: Relasped-reached end point | 7 | 12 |
| Withdrew: Protocol violation | 1 | 2 |
| Withdrew: Lost to follow-up | 3 | 4 |
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).
| weeks | Chamomile Extract | Placebo |
|---|---|---|
| Time to Relapse in Each Treatment Condition. | 11.4 ± 8.4 | 6.3 ± 3.9 |
The proportion of subjects in each treatment condition who relapsed after randomization
| Participants | Chamomile Extract | Placebo |
|---|---|---|
| The Proportion of Subjects in Each Treatment Condition Who Relapse. | 7 | 12 |
We will report the frequency, severity, and duration of treatment-emergent adverse events by treatment arm.
| Participants | Chamomile Extract | Placebo |
|---|---|---|
| Frequency, Severity, and Duration of Treatment-emergent Adverse Events. | 8 | 9 |
Discontinuation emergent signs and symptoms checklist (DESS) is a patient-rated measure of the presence and severity of discontinuation symptoms occurring after medication discontinuation. %
| Participants | Chamomile Extract | Placebo |
|---|---|---|
| # of subject had no new symptoms after randomizat | 31 | 33 |
| # of subject had >=1 new symptom after randomizati | 14 | 11 |
This is the # of subjects who discontinued the study during randomization phase due to other reasons.
| Participants | Chamomile Extract | Placebo |
|---|---|---|
| # Lost to Follow-up | 3 | 4 |
| # withdrawn due to non-compliance | 1 | 2 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Chamomile Extract | — | 0/46 (0%) | 8/46 (17.4%) |
| Placebo | — | 0/47 (0%) | 9/47 (19.1%) |
| Event | Chamomile Extract | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 3/46 | 0/47 |
| Dry mouthGeneral disorders | 2/46 | 0/47 |
| taste perversionProduct Issues | 1/46 | 2/47 |
| BruisingSkin and subcutaneous tissue disorders | 0/46 | 2/47 |
| Decreased platelet countBlood and lymphatic system disorders | 0/46 | 2/47 |
| CongestionRespiratory, thoracic and mediastinal disorders | 1/46 | 1/47 |
| DiarrheaGastrointestinal disorders | 1/46 | 0/47 |
| DizzinessNervous system disorders | 1/46 | 0/47 |
| DrowsinessNervous system disorders | 1/46 | 0/47 |
| FatigueGeneral disorders | 1/46 | 0/47 |
| Age, Categorical(Participants) | Chamomile Extract | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 40 | 42 | 82 |
| >=65 years | 6 | 5 | 11 |
| Age, Continuous(years) | Chamomile Extract | Placebo | Total |
|---|---|---|---|
| Mean | 49.2 ± 14.3 | 45.4 ± 16.1 | 47.3 ± 15.3 |
| Sex: Female, Male(Participants) | Chamomile Extract | Placebo | Total |
|---|---|---|---|
| Female | 34 | 31 | 65 |
| Male | 12 | 16 | 28 |
| Region of Enrollment(participants) | Chamomile Extract | Placebo | Total |
|---|---|---|---|
| United States | 46 | 47 | 93 |
Plan to share: No
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University of Pennsylvania