Rhodiola Rosea Therapy of Major Depressive Disorder

Phase 3

Completed

Conditions: Depression

Interventions: Dietary Supplement: Herbal extract
Other: Lactose monohydrate
Drug: Sertraline

Registration Number: NCT01098318

Lead Sponsor: University of Pennsylvania

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rhodiola rosea	Herbal extract	Herbal extract
Sugar pill	Lactose monohydrate	Lactose monohydrate
Sertraline	Sertraline	Conventional anti-depressant

Primary Outcome Measures

Name	Time	Method
Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (17-items) at Week 8 and Week 12.	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Depressive Symptoms as Measured by the Beck Depression Inventory	12 weeks	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.
The Clinical Global Impression (CGI) Severity and Change	12 weeks	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.
Change in Sexual Function	12 weeks	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.
Number of Participants With Suicide Ideation as Determined by the Columbia Suicide Form	12 weeks	Descriptive analysis of number of subjects in each treatment group who had suicidal ideation at baseline and WK12.
Number of Participants With Treatment Emergent Side Effects	12 weeks