RESTORE-LIFE: A Study to Assess Effectiveness and Efficiency of VNS Therapy in Patients With Difficult to Treat Depression.

Sponsor

LivaNova (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03320304

Collaborator

(none)

500

Enrollment

Locations

131.6

Anticipated Duration (Months)

27.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess short, mid and long-term clinical outcomes in patients with difficult to treat depression (such as patients with treatment resistant depression) treated with Vagus Nerve Stimulation (VNS) Therapy as adjunctive therapy.

Condition or Disease	Intervention/Treatment	Phase
Treatment Resistant Depression	Device: Vagal Nerve Simulation (VNS) Therapy

Detailed Description

The population under study comprises a real-world patient population with difficult to treat depression: patients diagnosed with unipolar or bipolar disorder with chronic or recurrent depression who fail to achieve an adequate response to standard psychiatric management.

The diagnosis of depression and comorbid disorders will be determined based on the Mini International Neuropsychiatric Interview (MINI).

A minimum of five hundred (500) patients will be implanted with a VNS Therapy System and up to eighty (80) sites may participate in this study.

Enrollment will take 8 years, based on competitive enrollment. For each subject a baseline visit will occur between 1 and 6 weeks before implant.

Once implanted with the device, subjects will be followed-up for a minimum of 36 months and a maximum of 60 months. The study may stop when the last subject has reached the 36 months follow-up.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Global PRospective, Multi-cEnter, ObServational Post-markeT Study tO Assess shoRt, Mid and Long-term Effectiveness and Efficiency of VNS Therapy® as Adjunctive Therapy in reaL-world patIents With diFficult to Treat dEpression.

Actual Study Start Date :

Dec 14, 2017

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Vagal Nerve Simulation (VNS) Therapy The aim of this study is to include patients with difficult to treat depression from a global "real world" (standard of care) population who are referred for treatment with VNS Therapy.	Device: Vagal Nerve Simulation (VNS) Therapy A VNS Therapy System used for vagus nerve stimulation and consisting of an implantable VNS Therapy generator, lead, and external programming system.

Arm

Intervention/Treatment

Vagal Nerve Simulation (VNS) Therapy

The aim of this study is to include patients with difficult to treat depression from a global "real world" (standard of care) population who are referred for treatment with VNS Therapy.

Device: Vagal Nerve Simulation (VNS) Therapy

A VNS Therapy System used for vagus nerve stimulation and consisting of an implantable VNS Therapy generator, lead, and external programming system.

Outcome Measures

Primary Outcome Measures

The primary endpoint of this study is response defined as reduction in Montgomery Åsberg Depression Rating Scale (MADRS) total score of at least 50% from baseline to 12 months post implant. [12 months]
MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Higher MADRS score indicates more severe depression. A 'Responder' is a subject that achieved ≥ 50% reduction from baseline in MADRS total score at the M12 assessment. A 'Non-Responder' is any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at the M12 assessment. No formal hypothesis testing is presented; all the proposed statistical tests are descriptive in nature. The Primary endpoint analysis as defined above will be done only on patients that are enrolled while in a major depressive episode (MDE); the cut off point for current MDE at time of implant will be a MADRS score of 20. For the patients with a MADRS score below 20 at time of enrollment, only the continuous change in MADRS can be described (as the MADRS can only worsen or stay the same).

Secondary Outcome Measures

Duration of response [through study completion, an average of 4 years]
computed as the difference between the first recorded date post baseline that response is achieved (MADRS reduction from baseline ≥ 50%) and the first date at which MADRS again increased to a level of <40% from baseline.
Change in MADRS [through study completion, an average of 4 years]
Change in MADRS over time
Cumulative response [through study completion, an average of 4 years]
Cumulative percentage of first-time MADRS responders (MADRS reduction from baseline ≥ 50%) at any post-baseline visit.
Cumulative remission [through study completion, an average of 4 years]
Cumulative percentage of subjects in remission (MADRS ≤9) at any post-baseline visit.
Changes in depression score As measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR). [through study completion, an average of 4 years]
The Quick Inventory of Depressive Symptomatology (QIDS-SR) is a 16-item, subject-completed questionnaire of the symptoms of mood and depression. The total score ranges from 0 to 27. A higher QIDS-SR score indicates a more severe depression.
Changes in mania score as measured by the Altman Self-Rating Mania Scale (ASRM)*. [through study completion, an average of 4 years]
*Optional assessments: to be done at selected sites only and based on investigator's clinical judgment to decide which subjects complete them. The Altman Self-rating Mania Scale (ASRM) is a 5-item self-reported diagnostic scale which can be used to assess the presence and severity manic and hypomanic symptoms, most commonly in patients diagnosed with bipolar disorder. The total score ranges from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.
Changes in Quality of Life as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) [through study completion, an average of 4 years]
The EuroQol five dimensions questionnaire (EQ-5D-5L) is a standardized 5-item subject completed questionnaire measuring generic health status and quality of life.
Changes in patient function as measured by the Work Productivity and Activity Impairment Scale (WPAI) [through study completion, an average of 4 years]
The Work Productivity and Activity Impairment Questionnaire (WPAI) is a subject self-reported 6-item questionnaire that measures impairments in work and activities. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Changes in Quality of Life and patient function as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) [through study completion, an average of 4 years]
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a standardized 16-item, self-report scale to assess the degree of enjoyment and satisfaction experienced by the subject during the past week.
Changes in suicidality as measured by item #10 of MADRS. [through study completion, an average of 4 years]
Item 10 on the Montgomery-Åsberg Depression Rating Scale (MADRS) scale assesses suicidal thoughts as representing the feeling that life is not worth living, that a natural death would be welcome, suicidal thoughts and preparations for suicide and is rated from 0 to 6. A score of ≥ 4 ('probably better off dead') is of particular interest.
Changes in suicidality as measured by item #12 of QIDS-SR. [through study completion, an average of 4 years]
For Item 12 of the Quick Inventory of Depressive Symptomatology (QIDS-SR), the subject assesses any thoughts of death or suicide over the previous 7 days on a 4- point scale; a score of ≥ 2 ('I think of suicide or death several times a week for several minutes') being of interest.
Changes in adjunctive antidepressant pharmacological treatment [through study completion, an average of 4 years]
All adjunctive concomitant antidepressant and psychotropic medications will be collected
Changes in adjunctive antidepressant non-pharmacological treatment [through study completion, an average of 4 years]
The following adjunctive non-pharmacological treatments will be collected: maintenance electroconvulsive therapy (ECT), Transcranial Magnetic Stimulation (TMS) and psychotherapy
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [through study completion, an average of 4 years]
The following adverse events will be collected: serious adverse events, deaths, VNS Therapy related adverse events and device deficiencies.
Changes in cognition [through study completion, an average of 4 years]
As measured by THINC-it® Tool*. *Optional assessments: to be done at selected sites only and based on investigator's clinical judgment to decide which subjects complete them.
Changes in anxiety as measured by the Generalized Anxiety Disorder Assessment (GAD 7)*. [through study completion, an average of 4 years]
*Optional assessments: to be done at selected sites only and based on investigator's clinical judgment to decide which subjects complete them. The Generalized Anxiety Disorder 7 (GAD-7) is a 7-item self-reported questionnaire for screening and severity measuring of generalized anxiety disorder (GAD). GAD-7 has seven items and uses a normative system of scoring. Assessment is indicated by the total score, which made up by adding together the scores for the scale all seven items.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be at least 18 years of age.
Have a documented primary diagnosis of chronic (>2 years) or recurrent (2 or more prior episodes) major depressive episode that has not adequately responded to an adequate number of antidepressant treatments, as per local medical standards. This diagnosis must be confirmed using the MINI.
Provide written Ethics Committee (EC) or Institutional Review Board (IRB) approved informed consent and Health Insurance Portability and Accountability Act (HIPAA, US only) authorization (as applicable according to local requirements).
Currently is receiving at least one antidepressant treatment (i.e., antidepressant drug, maintenance electroconvulsive therapy, or formal psychotherapy including supportive psychotherapy) or mood stabilizing treatment for bipolar patients (such as lithium, anticonvulsants, or atypical antipsychotics).
Able and willing to comply with the frequency of (outpatient) clinic visits and to reliably complete all the evaluations as specified in the study protocol.Hence based on the nature of their disease, the following patients should not be included: patients with mental retardation, current severe or significant substance/alcohol abuse, diagnosis of one or more schizophrenia-spectrum or other psychotic disorders, diagnosis of borderline or severe personality disorder as determined by clinical judgment which, in the investigator's opinion, would significantly interfere with subject's participation in the study)

Exclusion Criteria:

There are no exclusion criteria; the investigator should refer to the (local applicable) VNS Therapy Physician's Manual.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	AKH Allgemeines Krankenhaus der Stadt Wien	Vienna	Austria	1090
2	KU Leuven	Leuven	Belgium
3	Sozialstiftung Bamberg - Klinikum am Bruderwald	Bamberg	Germany
4	Universitätsklinikum Bonn	Bonn	Germany
5	LVR-Hospital Essen	Essen	Germany	45147
6	Universitätsklinikum Frankfurt	Frankfurt	Germany
7	Universitätsklinikum Freiburg	Freiburg	Germany
8	Universitätsmedizin Göttingen	Göttingen	Germany
9	Medizinische Hochschule Hannover	Hannover	Germany
10	Universitätsklinikum Jena	Jena	Germany
11	Universitätsklinikum Köln	Köln	Germany
12	Universitätsklinik Leipzig	Leipzig	Germany	04103
13	University Hospital Münster	Münster	Germany
14	Klinikum Wilhelmshaven	Wilhelmshaven	Germany
15	Glenfield hospital	Leicester	United Kingdom	LE3 9EJ
16	King's College London	London	United Kingdom
17	Academic Psychiatry Wolfson Research Centre	Newcastle Upon Tyne	United Kingdom
18	Mendip HTT / St Andrew's Ward	Wells	United Kingdom	BA5 1TH