Study of Maca Root to Treat Sexual Dysfunction Associated With the Treatment Regimen for Bipolar Disorder in Females

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00575328
• Collaborator: National Alliance for Research on Schizophrenia and Depression (Other)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this research study is to find out whether Maca Root is effective for treating sexual dysfunction in females that is caused by the treatment for bipolar disorder. An additional aim of the study is to document the safety and tolerability of maca root, as well as any potential side effects that it causes. We suspect that Maca Root will result in a significant reduction in sexual dysfunction when compared to a placebo group.

Condition or Disease	Intervention/Treatment	Phase
Sexual Dysfunction; Bipolar Disorder	Drug: Maca Root; Drug: Placebo	Phase 3

Detailed Description

The study seeks to enroll 80 patients with sexual dysfunction associated with their bipolar medication regimen over 24 months. Subjects were outpatient females between 18 and 80 years old with no significant symptoms of mania (Young Mania Rating Scale score<10), and who have been on a steady regimen of medications to treat bipolar disorder for at least 8 weeks, with a stable dose for at least 4 weeks. Subjects will be randomly assigned in a double blind manner to receive 3000 mg/day of maca root or identical placebo for 12 weeks to determine whether maca root is more effective than placebo for the treatment of sexual dysfunction associated with treatment regimens for bipolar disorder.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Maca root will be compared against inactive placebo as a treatment for sexual dysfunction induced by psychotropic drugs.Maca root will be compared against inactive placebo as a treatment for sexual dysfunction induced by psychotropic drugs.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: All subjects, investigators, and clinical assessors were blinded to the intervention.
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo Controlled Study of Maca Root for the Treatment of Sexual Dysfunction Associated With the Treatment Regimen for Bipolar Disorder in Females
• Actual Study Start Date: Feb 26, 2008
• Actual Primary Completion Date: Apr 26, 2010
• Actual Study Completion Date: Apr 26, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maca Root Subjects in this arm will be given 3g/day of Maca Root.	Drug: Maca Root; 3g/day of Maca Root for 12 weeks.; Other Names: Lepidium
Placebo Comparator: Placebo Subjects in this arm will receive inactive placebo.	Drug: Placebo; Placebo provided by research pharmacy daily for 12 weeks.; Other Names: Inactive placebo

Outcome Measures

Primary Outcome Measures

1. Reductions in Arizona Sexual Experience Scale (ASEX) Scores Over 12 Weeks of Treatment. [Biweekly from Baseline (week zero) to 12 weeks]

   The ASEX scale consists of five items rating sexual drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. The range of total score is from 5-30, with the higher scores indicating greater sexual dysfunction. Scores were obtained at baseline and at all biweekly assessment visits over the 12 weeks of treatment.

2. Reductions in Massachusetts General Hospital Sexual Dysfunction (MGH-SD) Inventory Scores Over 12 Weeks of Treatment. [Biweekly from Baseline (week zero) to 12 weeks]

   This instrument is composed of five items evaluating libido, sexual arousal or excitement, ability to achieve orgasm, ability to achieve and maintain an erection (for men only) and overall sexual satisfaction. Items are rated on a scale of 1 to 6 with a rating of 1 indicating greater than normal functioning and a rating of 6 indicating totally absent functioning. Possible total scores range from 5-30, with higher scores indicating greater pathology. Scores were obtained at baseline and at each biweekly assessment visit over 12 weeks of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject is female, age 18 to 80 years

• Subject has been on a steady regimen to treat bipolar disorder, including monotherapy with or any combination of antidepressants, mood stabilizers, atypical antipsychotics, or benzodiazepines, for at least 8 weeks; and is currently on a stable dose of that regimen for at least 4 weeks

• Subject is currently euthymic (Hamilton-D scale score < 10) and is without significant anxiety symptoms (Hamilton-A < 10). Her bipolar disorder must be in remission (Young Mania Rating Scale score < 10)

• Subject must have had no sexual dysfunction prior to taking psychotropic medications and there must be a clear temporal relationship between the sexual dysfunction and the treatment for bipolar disorder

• Subject must have been consistently experiencing at least one of the following criteria for at least 4 weeks, with distress or disability:

• Inability to have an orgasm, according to patient opinion

• Clinically significant orgasm delay with masturbation or intercourse

• Inability to attain or maintain until completion of sexual activity an adequate lubrication swelling response of sexual excitement

• Decreased libido according to patient opinion

• Subject must be having or had been having some form of regular sexual activity (masturbation, oral sex, intercourse) at least twice monthly prior to the bipolar treatment regimen and is willing to continue efforts at sexual activity at least once weekly for the duration of the study

• Subject must be in good general physical health

• Subject must be able to understand and communicate in English

• Subject must have given informed consent to participate in the study

Exclusion Criteria:

• Primary or prior diagnosis of a sexual disorder (other than the side effect of the bipolar medication or symptom of the bipolar disorder)

• Sexual dysfunction secondary to general underlying medical condition

• Penile, vaginal, clitoral or other sexual organ anatomical deformities

• Any uncontrolled psychiatric disorder

• Alcohol or substance abuse or dependence within the past six months

• Recent major relationship changes, disruption, or turmoil ongoing or anticipated which are unrelated to her sexual dysfunction

• Blood pressure outside the range of 90/50 - 170/100

• Known hyperprolactinemia

• Use of investigational drugs within previous 3 months or during study

• Current use of other drugs for sexual dysfunction or other therapies or medications to treat sexual dysfunction

• Current use of nefazodone

• Hormone replacement therapy, unless patient has been on stable dose of hormone therapy for at least 3 mo prior to the bipolar treatment regimen and had no sexual dysfunction while on the same hormone therapy regimen, and there is no change in the hormone replacement therapy during the study

• Pregnancy, lactating, or planning to become pregnant during the study

• Child bearing potential subjects unwilling and/or not prepared and/or who are judged unreliable to use an acceptable and verifiable form of contraception during the study

• Any clinically significant abnormality on the screening physical examination

• History of hormonal cancers

• Any medical or psychological condition or social circumstances that would impair subject's ability to participate reliably in the study, or that may increase the risk to subjects or others as a result of participating in this study

• Dyspareunia secondary to an inflammatory or anatomical condition

• Prior use of maca for at least two weeks

• Infection of the urogenital tract that may make sexual activity painful or difficult

• Subjects whose sexual partners are suffering from and/or receiving treatment for sexual dysfunction

• Receiving psychosexual or other therapy for sexual dysfunction and not willing to discontinue that treatment at screening

• Subjects who do not understand and communicate in English

• Subjects for whom sexual activity is inadvisable

• Subjects whose sexual dysfunction is considered to be situational

• Subjects not attempting some form of regular sexual activity at least twice monthly and at least once weekly during study visit intervals for duration of entire study

• Changes in bipolar medication and/or dose of medication within the last 4 weeks before baseline visit

• Participants on medications with a narrow therapeutic window or low therapeutic index for which small variations may be harmful given the lack of systematic experience with drug-supplement interactions (i.e. - cyclosporine, digoxin, warfarin, and antiretrovirals)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression Clinical and Research Program, Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Alliance for Research on Schizophrenia and Depression

Investigators

• Principal Investigator: Christina Dording, MD, Massachusetts General Hospital
• Study Director: David Mischoulon, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Mischoulon, MD, PhD, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00575328
• Other Study ID Numbers: 2007-P-001471
• First Posted: Dec 18, 2007
• Last Update Posted: Sep 25, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by David Mischoulon, MD, PhD, MD, Massachusetts General Hospital: Sexual Dysfunction; Bipolar Disorder
• Additional relevant MeSH terms: Disease; Bipolar Disorder

Study Results

Participant Flow

Recruitment Details	Female subjects with remitted bipolar disorder and sexual dysfunction associated with their bipolar medication treatment regimens were recruited from 2/26/2008 to 4/26/2010, all at the Massachusetts General Hospital Depression Clinical and Research Program.
Pre-assignment Detail	Subjects underwent a screening visit to determine eligibility. Those subjects deemed eligible returned a week later for a baseline visit, where eligibility was confirmed prior to treatment assignment. Subjects who for any reason no longer met entry criteria were discontinued and offered alternative treatment options.

Arm/Group Title	Maca Root	Placebo
Arm/Group Description	Subjects in this arm will be given 3g/day of Maca Root. Maca Root: 3g/day of Maca Root for 12 weeks.	Subjects in this arm will receive inactive placebo. Placebo: Placebo provided by research pharmacy daily for 12 weeks.
Period Title: Overall Study
STARTED	4	4
COMPLETED	1	2
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Maca Root	Placebo	Total
Arm/Group Description	Subjects in this arm will be given 3g/day of Maca Root. Maca Root: 3g/day of Maca Root for 12 weeks.	Subjects in this arm will receive inactive placebo. Placebo: Placebo provided by research pharmacy daily for 12 weeks.	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	4 100%	8 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37 (11)	37 (10)	37 (10)
Sex: Female, Male (Count of Participants)
Female	4 100%	4 100%	8 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	4 100%	3 75%	7 87.5%
Asian-Hispanic	0 0%	1 25%	1 12.5%
Region of Enrollment (Count of Participants)
United States	4 100%	4 100%	8 100%
Hamilton D-17 score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6 (3)	6 (2)	6 (2)
Young Mania Rating Scale score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2 (1.8)	1.5 (1.7)	1.8 (1.7)

Outcome Measures

1. Primary Outcome

Title	Reductions in Arizona Sexual Experience Scale (ASEX) Scores Over 12 Weeks of Treatment.
Description	The ASEX scale consists of five items rating sexual drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. The range of total score is from 5-30, with the higher scores indicating greater sexual dysfunction. Scores were obtained at baseline and at all biweekly assessment visits over the 12 weeks of treatment.
Time Frame	Biweekly from Baseline (week zero) to 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat sample. Subjects with at least one post baseline visit recorded with available data.

Arm/Group Title	Maca Root	Placebo
Arm/Group Description	Subjects in this arm will be given 3g/day of Maca Root. Maca Root: 3g/day of Maca Root for 12 weeks.	Subjects in this arm will receive inactive placebo. Placebo: Placebo provided by research pharmacy daily for 12 weeks.
Measure Participants	3	3
ASEX-Baseline Score	23.7 (1.5)	21.3 (0.6)
ASEX-Final Score	23.3 (3.8)	23 (2.8)
ASEX-Change in Score	-0.3 (4.2)	1.5 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maca Root, Placebo
	Comments	Null hypothesis: There will be no difference in clinical improvement (i.e. change in ASEX score) between treatment arms. No formal power analysis was carried out, given the small study sample.
	Type of Statistical Test	Superiority
	Comments	Analysis is a test of statistical significance to evaluate whether the results are consistent with the assumption of there being no difference in the clinical improvement (i.e. change in ASEX score) of the two treatments (null hypothesis).
Statistical Test of Hypothesis	p-Value	0.62
	Comments	No adjustment for multiple comparisons. P value for significance set a priori at P<0.05.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -8.7 to 12.3
	Parameter Dispersion	Type: Standard Deviation; Value: 3.3
	Estimation Comments
Other Statistical Analysis		The analysis is not truly informative, since the analyzable sample (n=6) was too small. Results should be viewed with caution.

2. Primary Outcome

Title	Reductions in Massachusetts General Hospital Sexual Dysfunction (MGH-SD) Inventory Scores Over 12 Weeks of Treatment.
Description	This instrument is composed of five items evaluating libido, sexual arousal or excitement, ability to achieve orgasm, ability to achieve and maintain an erection (for men only) and overall sexual satisfaction. Items are rated on a scale of 1 to 6 with a rating of 1 indicating greater than normal functioning and a rating of 6 indicating totally absent functioning. Possible total scores range from 5-30, with higher scores indicating greater pathology. Scores were obtained at baseline and at each biweekly assessment visit over 12 weeks of treatment.
Time Frame	Biweekly from Baseline (week zero) to 12 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat sample. Subjects with at least one post baseline visit recorded with available data.

Arm/Group Title	Maca Root	Placebo
Arm/Group Description	Subjects in this arm will be given 3g/day of Maca Root. Maca Root: 3g/day of Maca Root for 12 weeks.	Subjects in this arm will receive inactive placebo. Placebo: Placebo provided by research pharmacy daily for 12 weeks.
Measure Participants	3	3
MGH-SD Score-Baseline	21 (2)	18.7 (2.3)
MGH-SD Score-Final	16.7 (5.0)	18 (1.7)
Change in MGH-SD Score	-4.3 (6.1)	-0.7 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maca Root, Placebo
	Comments	Null hypothesis: There will be no difference in clinical improvement (i.e. change in MGH-SD score) between treatment arms. No formal power analysis was carried out, given the small study sample.
	Type of Statistical Test	Superiority
	Comments	Analysis is a test of statistical significance to evaluate whether the results are consistent with the assumption of there being no difference in the clinical improvement (i.e. change in MGH-SD score) of the two treatments (null hypothesis).
Statistical Test of Hypothesis	p-Value	0.38
	Comments	No adjustment for multiple comparisons. P value for significance set a priori at P<0.05.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -6.7 to 13.97
	Parameter Dispersion	Type: Standard Deviation; Value: 4.5
	Estimation Comments
Other Statistical Analysis		Analysis was not truly informative since the analyzable sample (n=6) was too small. Results should be interpreted with caution.

Adverse Events

Time Frame	2 years.
Adverse Event Reporting Description	All adverse events were systematically recorded and reported to the Institutional Review Board (IRB). All significant adverse effects were immediately reported upon their discovery and monitored through the following methods: 1) Going over any adverse events with the patient at each study visit 2) holding weekly meetings with the principal investigator and study staff team to review all safety and tolerability issues that were brought up.
Arm/Group Title	Maca Root		Placebo
Arm/Group Description	Subjects in this arm will be given 3g/day of Maca Root. Maca Root: 3g/day of Maca Root for 12 weeks.		Subjects in this arm will receive inactive placebo. Placebo: Placebo provided by research pharmacy daily for 12 weeks.
All Cause Mortality
	Maca Root		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Serious Adverse Events
	Maca Root		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/4 (0%)
Reproductive system and breast disorders
Menorrhagia	1/4 (25%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Maca Root		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		2/4 (50%)
Gastrointestinal disorders
Bloating	0/4 (0%)	0	1/4 (25%)	1
Heartburn symptom	0/4 (0%)	0	2/4 (50%)	2
Nausea	1/4 (25%)	1	0/4 (0%)	0
General disorders
Fatigue	1/4 (25%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Superficial laceration of leg	1/4 (25%)	1	0/4 (0%)	0
Nervous system disorders
Forgetfulness	1/4 (25%)	1	0/4 (0%)	0
Psychiatric disorders
Anxiety	1/4 (25%)	1	0/4 (0%)	0
Reproductive system and breast disorders
Vaginal bleeding	0/4 (0%)	0	2/4 (50%)	2
Respiratory, thoracic and mediastinal disorders
Influenza	1/4 (25%)	1	1/4 (25%)	1
Upper Respiratory Infection	1/4 (25%)	1	0/4 (0%)	0
Sore throat	0/4 (0%)	0	1/4 (25%)	1

Limitations/Caveats

Study was never completed due to low enrollment. Only 8 of a projected 80 subjects were randomized over a period of 2 years. Sample is too small to yield useful information.

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.