Rhodiola Rosea Therapy of Major Depressive Disorder

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01098318
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 58
• Location: 1
• Arms: 3
• Duration (Months): 37
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression	Dietary Supplement: Herbal extract; Drug: Sertraline; Other: Lactose monohydrate	Phase 3

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

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Rhodiola Rosea Therapy of Major Depressive Disorder
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. Number of Participants With Treatment Emergent Side Effects [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression Research Unit	Philadelphia	Pennsylvania	United States	19104-3309

Sponsors and Collaborators

• University of Pennsylvania
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Jun J. Mao, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Depression Research Unit-Department of Psychiatry Clinical Research Programs

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01098318
• Other Study ID Numbers: AT005230; R21AT005230
• First Posted: Apr 2, 2010
• Last Update Posted: Feb 22, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by University of Pennsylvania: Depression; Antidepressant Therapy; Herbal Treatment; Rhodiola rosea; Alternative Therapy
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Sertraline

Study Results

Participant Flow

Recruitment Details	There are actually 58 subjects who signed consents. However, one subject withdrew consent immediately after signed it due to change of mind. This subject didn't take any medication, therefore, only 57 subject received study intervention.

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Period Title: Overall Study
STARTED	20	19	18
COMPLETED	17	12	15
NOT COMPLETED	3	7	3

Baseline Characteristics

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill	Total
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily	Total of all reporting groups
Overall Participants	20	19	18	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.9 (16.9)	41.4 (14.6)	46.7 (15.2)	45.0 (15.5)
Sex: Female, Male (Count of Participants)
Female	8 40%	10 52.6%	8 44.4%	26 45.6%
Male	12 60%	9 47.4%	10 55.6%	31 54.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
HAM-D17@WK8	8 (5.4)	8.3 (4.5)	8.9 (6.5)
HAM-D17@WK12	7.9 (6)	7.8 (4.3)	8.5 (6.7)

2. Secondary Outcome

Title	The Clinical Global Impression (CGI) Severity and Change
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
WK12 CGI-Severity (Not ill and Borderline ill)	9 45%	6 31.6%	7 38.9%
WK12 CGI-C (Much improved and very much improved)	10 50%	7 36.8%	7 38.9%

3. Secondary Outcome

Title	Change in Depressive Symptoms as Measured by the Beck Depression Inventory
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
Mean (Standard Deviation) [scores on a scale]	-14.0 (10.0)	-13.7 (5.1)	-7.5 (12.2)

4. Secondary Outcome

Title	Change in Sexual Function
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled subjects were analyzed

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
Baseline	48	36	17
WK12	49	25.5	12

5. Secondary Outcome

Title	Number of Participants With Suicide Ideation as Determined by the Columbia Suicide Form
Description	Descriptive analysis of number of subjects in each treatment group who had suicidal ideation at baseline and WK12.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled subjects were analyzed

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
Baseline	6 30%	6 31.6%	9 50%
WK12	0 0%	0 0%	2 11.1%

6. Secondary Outcome

Title	Number of Participants With Treatment Emergent Side Effects
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All enrolled subjects were analyzed

Arm/Group Title	Rhodiola Rosea	Sertraline	Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily	Conventional anti-depressant Sertraline: 50-200 mg daily	Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
Measure Participants	20	19	18
Count of Participants [Participants]	6 30%	12 63.2%	3 16.7%

Adverse Events

Arm/Group Title	Rhodiola Rosea		Sertraline		Sugar Pill
Arm/Group Description	Herbal extract Herbal extract: 340-1,360 mg daily		Conventional anti-depressant Sertraline: 50-200 mg daily		Lactose monohydrate Lactose monohydrate: 1-4 capsules daily
All Cause Mortality
	Rhodiola Rosea		Sertraline		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rhodiola Rosea		Sertraline		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/19 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Rhodiola Rosea		Sertraline		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/20 (30%)		12/19 (63.2%)		3/18 (16.7%)
Gastrointestinal disorders
Nausea	1/20 (5%)	1	7/19 (36.8%)	10	1/18 (5.6%)	1
General disorders
Sexual dysfunction	1/20 (5%)	1	4/19 (21.1%)	7	0/18 (0%)	0
Dizziness	2/20 (10%)	2	0/19 (0%)	0	0/18 (0%)	0
Psychiatric disorders
Nervousness	2/20 (10%)	2	2/19 (10.5%)	2	2/18 (11.1%)	2

Limitations/Caveats

Subjects refuse to answer measures such as the RUSH sexual inventory and the CSSR. Therefore, no statistical analysis was performed on these. In addition, suicidal ideation (measured by CSSR) was captured in the AE form during the study peiod.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.