TMS: Beat the Blues in Pregnancy Study - Transcranial Magnetic Stimulation

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01492309
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 62
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if repetitive transcranial magnetic stimulation (TMS) will alleviate symptoms of major depressive disorder (MDD) in pregnant women.

TMS uses electromagnetic impulses to encourage neurons in the brain to communicate more effectively with one another. Effective neuron communication is thought to lead to the lessening of depressive symptoms. In this study subjects require daily TMS treatment for approximately four weeks.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Device: Active Transcranial Magnetic Simulation; Device: Sham Transcranial Magnetic Stimulation	N/A

Detailed Description

We hypothesize that there will be a decline in the Hamilton Rating Scale for Depression (HDRS-17) scores from the beginning to end of treatment. We expect that this decrease will be significantly greater in subjects receiving active transcranial magnetic stimulation (TMS) compared to those receiving placebo TMS. Treatment response will be defined as greater than 50% reduction in HDRS-17 score.

We also hypothesize that levels of Brain Derived Neurotrophic Factor (BDNF), a protein thought to regulate mood and cognitive functioning, will increase in subjects who respond to TMS treatment. We expect BDNF levels to increase by greater than or equal to 20% in those who respond to TMS. As previously stated, TMS response will be defined as a significant decrease (50% or greater) in the HDRS-17 from baseline to end of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transcranial Magnetic Stimulation (TMS) in Pregnant Women With Depressive Disorder
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Transcranial Magnetic Stimulation 38 pregnant women with MDD will be randomized to receive active 1 Hz right-sided dorsolateral prefrontal cortex (DLPFC) TMS.	Device: Active Transcranial Magnetic Simulation; Subjects will be given active TMS 5 days per week for 4 weeks for a total of 20 sessions. Each session will last approximately 10 minutes.; Other Names: Neuronetics 2100 CRS TMS System
Sham Comparator: Sham Transcranial Magnetic Stimulation 38 pregnant women with MDD will be randomized to receive sham transcranial magnetic stimulation.	Device: Sham Transcranial Magnetic Stimulation; Subjects will be given sham TMS 5 days per week for 4 weeks for a total of 20 sessions. The sham coil contains a shielding mechanism which diverts the magnetic field away from the patient. The sham treatment will last approximately 10 minutes.; Other Names: The eSham System

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment [Change score from baseline to test day 20 (after 20 days of intervention)]

   We measured changes in Hamilton Rating Scale for Depression (HDRS-17) scores from baseline to post-treatment. The HDRS-17 was administered on test days 1, 10, & 20. Scoring is based on the 17-item scale and scores of 0-7 is generally accepted to be within the normal range, indicating minimal to no depression; scores of 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale.

Secondary Outcome Measures

1. Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS) [Change in concentration from test day 1 to test day 20]

   We measured the levels of Brain Derived Neurotrophic Factor (BDNF) concentration across time. BDNF is a protein thought to regulate mood and cognitive functioning and research has suggested that levels may vary by severity of mood symptoms. We obtained BDNF values on test days 1 & 20.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects are capable of giving written informed consent and complying with all study procedures;

• Female age 18-39 years old at date of enrollment;

• Pregnant, weeks 14-34;

• Current Depressive Symptoms;

• No change in antidepressant medication at least two weeks prior to study entry if using an antidepressant.

Exclusion Criteria:

• Any alcohol or drug abuse/dependence over the 6 months prior to study entry;

• History of a seizure disorder in subject or first degree relative;

• Anti-psychotic, lithium, or anti-convulsant medications within 2 weeks of study enrollment;

• History of known brain lesions, or severe head trauma;

• Subjects with any metallic object implanted in the skull;

• Subjects with significant cardiac disease;

• Neurological or psychiatric disorders;

• Serious medical illnesses that may compromise patient safety or study conduct;

• Currently taking a drug with known potential for fetal toxicity;

• Previous pregnancy with an adverse fetal outcome;

• Current obstetrical complications

• Actively suicidal;

• History of depression unresponsive to treatment with electroconvulsive therapy (ECT).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn Center for Women's Behavioral Wellness	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Cynthia N Epperson, M.D., Penn Center for Women's Behavioral Wellness

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Program Website

Publications

• Kim D, O'Reardon JP. Editorial: the treatment of depression during pregnancy. Isr J Psychiatry Relat Sci. 2011;48(1):3-5.
• Kim DR, Epperson N, Paré E, Gonzalez JM, Parry S, Thase ME, Cristancho P, Sammel MD, O'Reardon JP. An open label pilot study of transcranial magnetic stimulation for pregnant women with major depressive disorder. J Womens Health (Larchmt). 2011 Feb;20(2):255-61. doi: 10.1089/jwh.2010.2353.
• Kim DR, Gonzalez J, O'Reardon JP. Pregnancy and depression: exploring a new potential treatment option. Curr Psychiatry Rep. 2009 Dec;11(6):443-6. Review.
• Kim DR, O'Reardon JP, Epperson CN. Guidelines for the management of depression during pregnancy. Curr Psychiatry Rep. 2010 Aug;12(4):279-81. doi: 10.1007/s11920-010-0114-x.
• Tjoa C, Pare E, Kim DR. Unipolar depression during pregnancy: nonpharmacologic treatment options. Womens Health (Lond). 2010 Jul;6(4):565-76. doi: 10.2217/whe.10.27. Review.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01492309
• Other Study ID Numbers: 812494; K23MH092399
• First Posted: Dec 14, 2011
• Last Update Posted: Apr 10, 2018
• Last Verified: Mar 1, 2018

• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by University of Pennsylvania: Major Depressive Disorder; Pregnancy; Brain Derived Neurotrophic Factor; Transcranial Magnetic Stimulation
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Pre-assignment Detail	22 participants were eligible at screening to be enrolled into the treatment arm of the study.

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD
Period Title: Overall Study
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active TMS	Sham TMS	Total
Arm/Group Description	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD	Total of all reporting groups
Overall Participants	11	11	22
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.13 (5.78)	26.41 (5.11)	28.27 (5.65)
Sex: Female, Male (Count of Participants)
Female	11 100%	11 100%	22 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Rating Scale for Depression (HDRS-17) Scores Pre- and Post- Treatment
Description	We measured changes in Hamilton Rating Scale for Depression (HDRS-17) scores from baseline to post-treatment. The HDRS-17 was administered on test days 1, 10, & 20. Scoring is based on the 17-item scale and scores of 0-7 is generally accepted to be within the normal range, indicating minimal to no depression; scores of 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the 17-point scale.
Time Frame	Change score from baseline to test day 20 (after 20 days of intervention)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD
Measure Participants	11	11
Mean (Standard Deviation) [difference in units on a scale]	-13.909 (5.224)	-9.091 (7.582)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active TMS, Sham TMS
	Comments	This analysis is based on a mixed model that can handle missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Change in Brain Derived Neurotrophic Factor (BDNF) With Active Transcranial Magnetic Simulation (TMS)
Description	We measured the levels of Brain Derived Neurotrophic Factor (BDNF) concentration across time. BDNF is a protein thought to regulate mood and cognitive functioning and research has suggested that levels may vary by severity of mood symptoms. We obtained BDNF values on test days 1 & 20.
Time Frame	Change in concentration from test day 1 to test day 20

Outcome Measure Data

Analysis Population Description

Only 4 participants from both the active and sham TMS groups were used in analysis because these participants had BDNF data at both time points. Furthermore, some samples were deemed unusable.

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD
Measure Participants	4	4
Mean (Standard Deviation) [pg/mL]	146.8775 (235.6441)	40.0550 (131.9466)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active TMS, Sham TMS
	Comments	This analysis is based on a mixed model that can handle missing data.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.425
	Comments
	Method	Regression, Logistic
	Comments

Adverse Events

Arm/Group Title	Active TMS		Sham TMS
Arm/Group Description	11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD		11 pregnant women in their 2nd or 3rd trimester with a primary diagnosis of MDD
All Cause Mortality
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Serious Adverse Events
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		0/11 (0%)
Pregnancy, puerperium and perinatal conditions
Preterm Birth	3/11 (27.3%)	3	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/11 (36.4%)		1/11 (9.1%)
Nervous system disorders
Headaches	4/11 (36.4%)	17	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.