Reclaim Deep Brain Stimulation Clinical Study for Treatment-Resistant Depression

• Sponsor: MedtronicNeuro (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00837486
• Collaborator: (none)
• Enrollment: 30
• Locations: 5
• Arms: 2
• Duration (Months): 49.9
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Medtronic, Inc. sponsored an investigational study of the Reclaim™ Deep Brain Stimulation (DBS) System in people that have treatment-resistant depression. Depression is a mood disorder and a serious medical condition that affects millions of Americans. Depressive symptoms may include loss of interest in things typically enjoyed; decreased energy levels; difficulty concentrating or making decisions; restlessness; and feelings of pessimism, hopelessness, and worthlessness. Treatment-resistant depression is a chronic and severe form of depression characterized by failure to respond to traditional forms of treatment, such as antidepressant medications and electroconvulsive therapy. Treatment-resistant depression significantly impacts quality of life, productivity, and is a major contributor of disability world-wide.

This randomized, double-blind, sham stimulation-controlled, multi-center, prospective, parallel design study used deep brain stimulation technology to test whether active bilateral stimulation can safely and effectively improve depressive symptoms in patients with treatment-resistant depression compared to sham stimulation.

Participants meeting criteria for the study were implanted with the Reclaim DBS System. Participants in the active group, who received active stimulation, were compared to the control group, who received sham stimulation, during the 16-week blinded-treatment phase. All participants were monitored for changes in depressive symptoms. After the blinded-treatment phase, all participants received active stimulation.

Candidates for the trial were adults who had major depressive disorder and had not responded to several treatments for depression. Participants in the study continued to receive their current antidepressant medications while participating in the trial.

Condition or Disease	Intervention/Treatment	Phase
Depression	Device: Reclaim™ DBS System	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Reclaim Deep Brain Stimulation Clinical Study for Treatment-Resistant Depression
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Group - Active Stimulation Receive active stimulation with Reclaim™ DBS System	Device: Reclaim™ DBS System
Sham Comparator: Control Group - Sham Stimulation Receive sham stimulation with Reclaim™ DBS System	Device: Reclaim™ DBS System

Outcome Measures

Primary Outcome Measures

1. Responders [Baseline to 16 weeks]

   Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response.

Secondary Outcome Measures

1. Depression Change [Baseline to 16 weeks]

   Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Improvement is measured by the groups' mean percent change in MADRS score. An improvement is represented by a decline in MADRS (a negative percent change).

2. Quality of Life Change [Baseline to 16 weeks]

   Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF); total score can range from 0 to 100 with higher scores indicating a better quality of life. Improvement is measured by the groups' mean change in Q-LES-Q-SF score. An improvement is represented by an increase in Q-LES-Q-SF (a positive change).

Other Outcome Measures

1. Long-term Open-label Responders [at the 24-month visit]

   This measure is for long-term, open-label stimulation. Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. All enrolled participants are included in the analysis, even if they withdrew early. Participants that withdrew early are counted as non-responders.

2. Therapy-related Adverse Events [from enrollment to study closure (average follow-up of 36 months)]

   Adverse events related to the device, implant procedure, and/or stimulation are reported. Events with a prevalence of greater than 5% of subjects are reported. This measure describes the experience of all study participants (both Active and Control Groups combined), and includes the operative, blinded-treatment,and the long-term open-label follow-up phases combined. Active Group participants began therapy after randomization, while Control Group participants began therapy after 16 weeks of sham stimulation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Consent to participate in screening and study procedures by signing and dating the Informed Consent Form

• Are diagnosed with major depressive disorder (MDD)

• Have tried at least 4 different treatments, for example antidepressant medications, combinations of antidepressant medications, and/or electroconvulsive therapy (ECT)

• Screening MADRS score ≥ 28

• Have had the current major depressive episode persist for at least 2 years

• Females, if of child-bearing potential, must be using an acceptable method of birth control

Exclusion Criteria:

• Females: Currently pregnant

• Currently enrolled in or plan to enroll in any concurrent drug and/or device study that may confound the results of this study

• Have a neurological condition that may jeopardize the safety or the conduct of the study

• Have any medical conditions unsuitable for undergoing DBS surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Charlestown	Massachusetts	United States	02129
2	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
3	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
4	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
5	Butler Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• MedtronicNeuro

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedtronicNeuro
• ClinicalTrials.gov Identifier: NCT00837486
• Other Study ID Numbers: 1626; G080033
• First Posted: Feb 5, 2009
• Last Update Posted: May 28, 2015
• Last Verified: May 1, 2015

• Keywords provided by MedtronicNeuro: Treatment Resistant Depression; Treatment Refractory Depression; Deep Brain Stimulation; Depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant

Study Results

Participant Flow

Arm/Group Title	Active Group-Active Stimulation	Control Group-Sham Stimulation
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.	Receive sham stimulation during the first 16 weeks after device implant.
Period Title: Blinded-treatment Phase
STARTED	16	14
COMPLETED	15	14
NOT COMPLETED	1	0
Period Title: Blinded-treatment Phase
STARTED	29	0
COMPLETED	24	0
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Active Group-Active Stimulation	Control Group-Sham Stimulation	Total
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.	Receive sham stimulation during the first 16 weeks after device implant.	Total of all reporting groups
Overall Participants	16	14	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.6 (14.4)	48.9 (8.9)	47.7 (12.0)
Sex: Female, Male (Count of Participants)
Female	8 50%	5 35.7%	13 43.3%
Male	8 50%	9 64.3%	17 56.7%
Region of Enrollment (participants) [Number]
United States	16 100%	14 100%	30 100%
Baseline depression score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	37.0 (5.1)	36.4 (3.3)	36.7 (4.3)

Outcome Measures

1. Primary Outcome

Title	Responders
Description	Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

29 of the 30 subjects are included in this analysis. One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Arm/Group Title	Active Group-Active Stimulation	Control Group-Sham Stimulation
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.	Receive sham stimulation during the first 16 weeks after device implant.
Measure Participants	15	14
Number [participants]	3 18.8%	2 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active Group-Active Stimulation, Control Group-Sham Stimulation
	Comments	The study originally required a sample size of 208 subjects in order to have 90% power to detect a statistically significant difference between the responder rate of the active and control groups. With this 30-subject cohort, and only 29 subjects completing the blinded-treatment phase per protocol, the comparison of response rates was not adequately powered. The P-value is presented only to describe the outcomes of the two groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.53
	Comments	one-sided P-value per protocol responder rates: Active Group = 20.0%, Control Group = 14.3%
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Depression Change
Description	Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Improvement is measured by the groups' mean percent change in MADRS score. An improvement is represented by a decline in MADRS (a negative percent change).
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Arm/Group Title	Active Group-Active Stimulation	Control Group-Sham Stimulation
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.	Receive sham stimulation during the first 16 weeks after device implant.
Measure Participants	15	14
Mean (Standard Deviation) [percentage change from baseline]	-19.6 (34.9)	-24.6 (28.8)

3. Secondary Outcome

Title	Quality of Life Change
Description	Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF); total score can range from 0 to 100 with higher scores indicating a better quality of life. Improvement is measured by the groups' mean change in Q-LES-Q-SF score. An improvement is represented by an increase in Q-LES-Q-SF (a positive change).
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.

Arm/Group Title	Active Group-Active Stimulation	Control Group-Sham Stimulation
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.	Receive sham stimulation during the first 16 weeks after device implant.
Measure Participants	15	14
Mean (Standard Deviation) [change from baseline score]	10.2 (24.8)	9.8 (18.8)

4. Other Pre-specified Outcome

Title	Long-term Open-label Responders
Description	This measure is for long-term, open-label stimulation. Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. All enrolled participants are included in the analysis, even if they withdrew early. Participants that withdrew early are counted as non-responders.
Time Frame	at the 24-month visit

Outcome Measure Data

Analysis Population Description

29 participants started the the Long-Term Follow-up Phase and 24 completed the phase, but all 30 enrolled participants are included in the analysis. Participants that withdrew early are counted as non-responders.

Arm/Group Title	Long-term Open-label Treatment
Arm/Group Description	All subjects received open-label active stimulation after the 16 week blinded-treatment phase.
Measure Participants	30
Number [participants]	7 43.8%

5. Other Pre-specified Outcome

Title	Therapy-related Adverse Events
Description	Adverse events related to the device, implant procedure, and/or stimulation are reported. Events with a prevalence of greater than 5% of subjects are reported. This measure describes the experience of all study participants (both Active and Control Groups combined), and includes the operative, blinded-treatment,and the long-term open-label follow-up phases combined. Active Group participants began therapy after randomization, while Control Group participants began therapy after 16 weeks of sham stimulation.
Time Frame	from enrollment to study closure (average follow-up of 36 months)

Outcome Measure Data

Analysis Population Description

All enrolled participants are included in the analysis.

Arm/Group Title	All Enrolled Subjects
Arm/Group Description	The 30 subjects were followed an average of 36 months after enrollment.
Measure Participants	30
Device - Implant site pain	7 43.8%
Device - Paraesthesia	4 25%
Procedure - Implant site pain	8 50%
Procedure - Implant site infection	5 31.3%
Procedure - Dermatitis contact	2 12.5%
Procedure - Face oedema	2 12.5%
Procedure - Headache	2 12.5%
Procedure - Hypersensitivity	2 12.5%
Stimulation - Insomnia	15 93.8%
Stimulation - Depression	8 50%
Stimulation - Hypomania	8 50%
Stimulation - Irritability	8 50%
Stimulation - Anxiety	7 43.8%
Stimulation - Fatigue	6 37.5%
Stimulation - Headache	6 37.5%
Stimulation - Agitation	5 31.3%
Stimulation - Sleep disorder	5 31.3%
Stimulation - Disturbance in attention	4 25%
Stimulation - Suicidal ideation	4 25%
Stimulation - Disinhibition	3 18.8%
Stimulation - Memory impairment	3 18.8%
Stimulation - Paraesthesia	3 18.8%
Stimulation - Energy increased	2 12.5%
Stimulation - Impulsive behaviour	2 12.5%
Stimulation - Nausea	2 12.5%
Stimulation - Thinking abnormal	2 12.5%
Stimulation - Weight increased	2 12.5%

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	Adverse event results for the blinded-treatment phase only. All randomized subjects were included in adverse event summaries.
Arm/Group Title	Active Group-Active Stimulation		Control Group-Sham Stimulation
Arm/Group Description	Receive active stimulation during the first 16 weeks after device implant.		Receive sham stimulation during the first 16 weeks after device implant.
All Cause Mortality
	Active Group-Active Stimulation		Control Group-Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active Group-Active Stimulation		Control Group-Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		4/14 (28.6%)
Infections and infestations
Wound infection staphylococcal	0/16 (0%)		1/14 (7.1%)
Injury, poisoning and procedural complications
Neurostimulator protrusion	0/16 (0%)		1/14 (7.1%)
Psychiatric disorders
Depression	1/16 (6.3%)		3/14 (21.4%)
Suicidal ideation	1/16 (6.3%)		0/14 (0%)
Disinhibition	1/16 (6.3%)		0/14 (0%)
Vascular disorders
Femoral arterial stenosis	1/16 (6.3%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Active Group-Active Stimulation		Control Group-Sham Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)		14/14 (100%)
Ear and labyrinth disorders
Tinnitus	0/16 (0%)		1/14 (7.1%)
Eye disorders
Eye pain	1/16 (6.3%)		0/14 (0%)
Ocular hyperaemia	1/16 (6.3%)		0/14 (0%)
Gastrointestinal disorders
Abdominal pain	1/16 (6.3%)		0/14 (0%)
Dysphagia	1/16 (6.3%)		0/14 (0%)
Toothache	1/16 (6.3%)		0/14 (0%)
Constipation	0/16 (0%)		1/14 (7.1%)
General disorders
Implant site pain	4/16 (25%)		2/14 (14.3%)
Fatigue	3/16 (18.8%)		0/14 (0%)
Drug withdrawal syndrome	1/16 (6.3%)		1/14 (7.1%)
Energy increased	1/16 (6.3%)		0/14 (0%)
Allodynia	0/16 (0%)		1/14 (7.1%)
Infections and infestations
Influenza	1/16 (6.3%)		1/14 (7.1%)
Upper respiratory tract infection	2/16 (12.5%)		0/14 (0%)
Gastroenteritis viral	1/16 (6.3%)		1/14 (7.1%)
Localised infection	0/16 (0%)		2/14 (14.3%)
Fungal infection	0/16 (0%)		1/14 (7.1%)
Nasopharyngitis	0/16 (0%)		1/14 (7.1%)
Injury, poisoning and procedural complications
Fall	1/16 (6.3%)		3/14 (21.4%)
Animal bite	0/16 (0%)		1/14 (7.1%)
Back injury	0/16 (0%)		1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Bunion	1/16 (6.3%)		0/14 (0%)
Bursitis	0/16 (0%)		1/14 (7.1%)
Muscle spasms	0/16 (0%)		1/14 (7.1%)
Osteoarthritis	0/16 (0%)		1/14 (7.1%)
Rotator cuff syndrome	0/16 (0%)		1/14 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	1/16 (6.3%)		0/14 (0%)
Nervous system disorders
Headache	2/16 (12.5%)		1/14 (7.1%)
Tremor	1/16 (6.3%)		1/14 (7.1%)
Cognitive disorder	1/16 (6.3%)		0/14 (0%)
Hypersomnia	1/16 (6.3%)		0/14 (0%)
Hyporeflexia	1/16 (6.3%)		0/14 (0%)
Somnolence	1/16 (6.3%)		0/14 (0%)
Transient ischaemic attack	1/16 (6.3%)		0/14 (0%)
Balance disorder	0/16 (0%)		1/14 (7.1%)
Paraesthesia	0/16 (0%)		1/14 (7.1%)
Restless legs syndrome	0/16 (0%)		1/14 (7.1%)
Psychiatric disorders
Depression	4/16 (25%)		0/14 (0%)
Insomnia	4/16 (25%)		3/14 (21.4%)
Irritability	3/16 (18.8%)		0/14 (0%)
Suicidal ideation	1/16 (6.3%)		0/14 (0%)
Disinhibition	1/16 (6.3%)		0/14 (0%)
Hypomania	2/16 (12.5%)		0/14 (0%)
Sleep disorder	1/16 (6.3%)		1/14 (7.1%)
Mania	1/16 (6.3%)		0/14 (0%)
Early morning awakening	0/16 (0%)		1/14 (7.1%)
Purging	0/16 (0%)		1/14 (7.1%)
Reproductive system and breast disorders
Adnexa uteri mass	1/16 (6.3%)		0/14 (0%)
Menstruation irregular	0/16 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)		0/14 (0%)
Sinus congestion	1/16 (6.3%)		0/14 (0%)
Upper respiratory tract congestion	0/16 (0%)		1/14 (7.1%)
Vascular disorders
Hypertension	3/16 (18.8%)		0/14 (0%)

Limitations/Caveats

With this 30-subject cohort, and only 29 subjects completing the blinded-treatment phase per protocol, the comparisons of response rates and improvements were not adequately powered.

More Information

Certain Agreements

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

The disclosure restrictions on the PI allow for the sponsor to review results communications prior to public release and to embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to sponsor for review. The sponsor is also allowed to require changes for technical correctness and to protect confidential information, copyrightable or patentable material; and when reasonably requested, extend the embargo up to an additional 90 days.