Rhodiola Rosea Therapy of Major Depressive Disorder

Study Overview
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Brief Summary
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Prior research has shown that Rhodiola rosea may be an effective, short-term, anti-depressant therapy. This study will examine the anti-depressant effect of Rhodiola rosea vs. a conventional, anti-depressant drug in the treatment of major depression.

Detailed Description
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We will study the antidepressant action of R. rosea in patients with MDD. Depression affects more than a billion people world wide, and is now recognized as one of the most disabling medical conditions. It accounts for more than 11% of the total disease burden worldwide, and can result in devastating consequences and functional impairment exceeded only by that of cancer and cardiovascular disease. It results in substantial social, occupational, and personal disability and in increased medical co-morbidity and death by suicide. It is considered to be a multi-systemic disorder characterized by neurotransmitter, neuroendocrine, immunologic, and autonomic, and infectious disturbances. Although the development of antidepressant drug therapy has simplified the treatment of MDD, a substantial segment of the world's population remains untreated for economic, cultural, or personal reasons. As a result, many individuals seek CAM for relief of their symptoms. The identification of effective CAM therapies for MDD is of public health relevance. R. rosea belongs to the family Crassulaceae, and has a long history as a folk remedy for enhancing physical and emotional endurance. Its adaptogen, or preventive, properties have also led to its use in treating cancer, infection, depression, and other nervous system disorders. Several animal and human studies suggest that R. rosea may have antidepressant properties. For specific aim #1, we will ask: Is R. rosea a safe and effective short-term therapy (vs. sertraline and placebo) for patients with MDD? To answer this question, patients meeting DSM IV criteria for mild to moderate MDD will be enrolled in a 12-week, randomized, double-blind, placebo-controlled, parallel group, dose-escalation study of R. rosea extract 340-1,360 mg daily vs. sertraline 50-200 mg daily. The primary outcome measure will be change over time in the 17-item Hamilton Depression Rating score. We hypothesize that R. rosea will have superior efficacy vs. placebo and comparable efficacy vs. sertraline. For specific aim #2, we will ask: Does R. rosea therapy result in a favorable tolerability and quality of life (QOL) profile vs. sertraline and placebo? To answer this question, we will obtain safety and QOL measures across treatment conditions that include: (i) frequency, duration, and severity of adverse events, (ii) frequency of serious adverse events, (iii) frequency of dosage reduction, (iv) frequency of treatment discontinuation, and (v) QOL and sexual performance measures. We hypothesize that R. rosea will have a superior tolerability profile vs. sertraline, and similar tolerability vs. placebo. We further hypothesize that R. rosea will have superior QOL and sexual performance ratings vs. sertraline and placebo. Results from this study will be used to inform future research hypotheses and to estimate the effect size necessary to power a future, large scale study.

Official Title
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Rhodiola Rosea Therapy of Major Depressive Disorder

Conditions
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Depression

Intervention / Treatment
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* Dietary Supplement: Herbal extract
* Drug: Sertraline
* Other: Lactose monohydrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (all races and ethnicity) ≥ 18 years old DSM IV Axis I diagnosis of mild to moderate Major Depressive Disorder Baseline CGI/S rating of 3 ('mild') or 4 ('moderate') Baseline Hamilton Depression Rating score ≥ 10 Not receiving other antidepressant therapy Able to provide signed informed consent Exclusion Criteria: Patients < 18 years old Current primary DSM IV Axis I diagnosis other than Major Depressive Disorder CGI/S rating of 5 ('marked'), 6 ('severe') or 7 ('very severe') Actively suicidal or requiring hospitalization Uncontrolled medical condition Pregnant or nursing women Women of child-bearing potential not using a medically acceptable form of contraception Concurrent use of herbal remedies or mineral supplements [Note: Use of mineral supplements prescribed for medical purposes (e.g., osteoporosis) will not be excluded] Current use of chemotherapy or other medication (e.g., interferon) known to produce fatigue or mood changes Known sensitivity to R. rosea or sertraline History of non-response to sertraline in the current depressive episode

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rhodiola rosea<br>Herbal extract | Dietary Supplement: Herbal extract<br>* 340-1,360 mg daily<br>* Other names: Golden root;|
| Active Comparator: Sertraline<br>Conventional anti-depressant | Drug: Sertraline<br>* 50-200 mg daily<br>* Other names: Zoloft;|
| Placebo Comparator: Sugar pill<br>Lactose monohydrate | Other: Lactose monohydrate<br>* 1-4 capsules daily<br>* Other names: Milk powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (17-items) at Week 8 and Week 12. | Hamilton Depression Rating Scale (HAM-D) is a validated, clinician-rated instrument for ascertaining the severity of MDD symptoms. The 28-item Hamilton Depression Rating Scale was used to determine the primary outcome of 17-item HAM-D score. The HAM-D will serves as the primary outcome measure. HAM-D17 score ranges from 0 to 68. Higher score indicates more depressed symptom. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Clinical Global Impression (CGI) Severity and Change | A clinician-rated measure of global symptom severity (CGI/S) and symptom change (CGI/C) of MDD. Severity was rated as Not ill; Borderline ill; Mild; Moderate; Moderately severe; Severe and Extremely severe. Global change was rates as Very much improved; Much improved; Minimally improved; Unchanged;Minimally worse;Much worse and Very much worse. Here in severity, we reported the N(%) of subjects who were not ill or borderline ill. In change, we reported N(%) of subjects who were Very much improved or Much imp[roved.Subjects started the study with mild to moderate MDD (moderate or above rating in the CGI-S). At WK12, the #/% of subjects in each treatment group who were not ill at WK12 (CGI-S) and who had much improved or very much improved at WK12 (CGI-C) was reported. | 12 weeks | 
| Change in Depressive Symptoms as Measured by the Beck Depression Inventory | All enrolled subjects were analyzed. Mean change in Beck Depression Inventory (BDI) total scores were reported. BDI is a self-reported outcome measuring the severity of depression. A negative # means a reduction in BDI score at the end of treatment compared to baseline which represents an improvement in depression symptoms. BDI total score ranges from 0-63. BDI score of 1-16 represents low level of depression;17-30 represents moderate level of depression; >=31 represents significant level of depression. A reduction in the BDI score represents improvement in the depression symptoms. | 12 weeks | 
| Change in Sexual Function | This is a patient completed rating of sexual function and satisfaction. It is used to assess current sexual health and changes in sexual health over time measured by the overall sexual satisfaction score. The reported score is the overall degree of sexual satisfaction attained. The score ranges from 0 to 100. Higher score indicates more sexual satisfaction. | 12 weeks | 
| Number of Participants With Suicide Ideation as Determined by the Columbia Suicide Form | Descriptive analysis of number of subjects in each treatment group who had suicidal ideation at baseline and WK12. | 12 weeks | 
| Number of Participants With Treatment Emergent Side Effects |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Antidepressant Therapy, Herbal Treatment, Rhodiola rosea, Alternative Therapy