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出境医 / 临床实验 / Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment
Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment
Study Description
Brief Summary:
Methadone maintenance treatment (MMT) is one of the main forms of treatments for opioid dependence. Despite its effectiveness and widespread use, people will experience withdrawal if daily dose is insufficient or missed, promoting reluctance to attempt detoxification. In addition, methadone is a full opioid agonist which can induce respiratory depression or sedation without ceiling level, so overdose usage can be fatal. Hence, an alternative therapy is needed to completely reduce the carving for drugs and to relieve the negative affective sate caused by withdrawal.
Deep brain stimulation (DBS) is a reasonable treatment approach for addiction. Since 2009 the first case report emerged, the nucleus accumbens (NAc) is still the only brain target to be investigated in clinical case series of DBS for alcohol and heroin addiction.
This research will mainly investigate the effectiveness and safety of NAc-DBS for patients with methadone maintenance treatment. The investigators will also explore the influence of NAc-DBS on brain activity and cognition.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Addiction Opiate | Procedure: Bilateral surgical implantation of DBS system to Nucleus Accumbens | Not Applicable |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 12 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment |
| Actual Study Start Date : | May 13, 2019 |
| Estimated Primary Completion Date : | June 1, 2021 |
| Estimated Study Completion Date : | June 1, 2021 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: DBS
All subjects will undergo bilateral surgical implantation of DBS system in the Nucleus Accumbens. The DBS system will be active at two days after surgery.
|
Procedure: Bilateral surgical implantation of DBS system to Nucleus Accumbens
We plan to use the SceneRay 1242 (SceneRay, SuZhou, China) electrode with a diameter of 1.27 mm and 4 contacts. The SceneRay 1242 electrode combined with the SceneRay 1181 implantable pulse generator has the advantage of adaptive coverage area for the Ventral Capsule/Ventral Striatum, enabling simultaneous implantation in the nucleus accumbens (NAc; 2 ventral contacts) and the anterior limb of the internal capsule (ALIC; 2 dorsal contacts) with independently programmed parameters such as frequency, amplitude, and voltage; and remote and wireless programing, which allows for convenient and prompt adjustments in emergency situations. The contact length is 3.0 mm and the spacings between the ventral and dorsal contacts are 2 mm, 4 mm, and 4 mm, respectively, spanning a total length of 22.5 mm (3 + 2 + 3 + 4 + 3 + 4 + 3 mm, with 0.5 mm projecting from the electrode tip).
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Outcome Measures
Primary Outcome Measures :
- Changes in Methadone dose [ Time Frame: Baseline (preoperative),1 month, 3 months,6 months,9 months, 12 months ]The volume of daily methadone the patients used.
Secondary Outcome Measures :
- Hamilton Depression Scale(HAMD-17) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months, 9 months, 12 months ]17 items, Total scores<7: normal; 7<Total scores≤17: possible depression; 17<Total scores≤24: definite depression; Total score>24: severe depression
- Hamilton Anxiety Scale (HAMA) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months ]14 items, Total scores<6: normal; 7<Total scores≤14: possible anxiety; 14<Total scores≤21:definite anxiety; Total score>21: severe anxiety
- Young Manic Rating Scale (YMRS) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months ]The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition.
- Monitoring of Side Effects Scale (MOSES) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months ]To evaluate side effects. The higher score means more severity of side effects.
- Changes in Subjective Opiate Withdrawal Scale(SOWS) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months ]Subjective Opiate Withdrawal Scale is a 16-item self-reported scale assessing severity of opiate withdrawal. Each item is rated on a 5-point Likert scale, ranging form 0(not at all) to 4(extremely).
- Obsessive compulsive drug use scale(OCDUS) [ Time Frame: Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months ]Obsessive compulsive drug use scale is a 13-item self-rating scale measuring opiate craving. The total score ranges from 0 to 52. The higher score indicates stronger carving.
- The MOS item short from health survey (SF-36) [ Time Frame: Baseline(preoperative),1 month, 3 months,6 months,9 months, 12 months ]36 items. To evaluate the quality of life and the higher score indicates better quality of life.
- World Health Organization Quality of Life-BREF (WHO-BREF) [ Time Frame: Baseline(preoperative),1 month, 3 months,6 months,9 months, 12 months ]26 items. The higher score means the better quality of life.
- Fagerstrom Test for Nicotine Dependence assessment (FTND) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]To evaluate Nicotine Dependence. The higher of scores indicates higher level of Nicotine Dependence
- Beck depression inventory(BDI) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]The BDI contains 21 questions, each answer scored on a scale value of 0 to 3. 0-13: minimal depression;14-19:mild depression; 20-28:moderate depression; and 29-63:severe depression. Higher total score indicate more severe depressive symptoms.
- Beck anxiety inventory(BAI) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]The BAI contains 21 questions, each answer scored on a scale value of 0 to 3. 0-21: mild anxiety;22-35: moderate anxiety;36-63:severe anxiety. Higher total score indicate more severe anxiety symptoms.
- Perceived stress scale(PSS-10) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]The PSS-10 is a classic stress assessment instrument. Each item is rated on a 5-likert scale ranging form 0(never) to 4(often). Higher score indicate more severity of stress symptom.
- Twenty Item Positive and Negative Affect Schedule (PANAS) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]The PANAS contains two subscales: positive and negative subscale. Each item is rated on a 5-likert scale ranging from 1(Not at all) to 5(severely, it bothered me a lot).
- Work and Social Adjustment Scale(WSAS) [ Time Frame: Baseline(preoperative),1 month, 3months,6months,9 months, 12 months ]Self-rated scale. The maximum score of the WSAS is 40, lower scores are better.
- Cognitive performance [ Time Frame: Baseline(preoperative),6 months,12 months ]Cognitive performance is measured by a series of tasks which include stop signal task, paired associated memory, spatial working memory, stocking of Cambridge, intra-extra dimensional set shift, Bart, Beads, Delay discounting task, model-based and model-free task, avoid-approach task, dot-probe task, drug rating task.
- Brain activity [ Time Frame: Baseline(preoperative), 6 months,12 months ]PET(Positron Emission Tomography) or fMRI(functional Magnetic Resonance Imaging) are used in this study.
Other Outcome Measures:
- Barratt impulsiveness scale [ Time Frame: Baseline(preoperative) ]The Barratt Impulsiveness Scale is a questionnaire designed to assess the personality/behavioral construct of impulsiveness which is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. It has three 2nd order facets which are attentional, motor and non-planning. Each facet has 10 items. Higher score means greater impulsivity.
- UPPS-P impulsive behavior scale [ Time Frame: Baseline(preoperative) ]The UPPS-P Impulsive Behavior Scale is a 59-item questionnaire assessing impulsive personality traits. Each item is rated on a 4-point scale ranging from 1 (agree strongly) to 4 (disagree strongly) to indicate subject's agreement with statements. This scale includes the following five subscales: negative urgency (NU), lack of premeditation (LPM), lack of perseverance (LPS), sensation seeking (SS) and positive urgency (PU). Higher score represents a greater level of impulsivity.
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- MINI diagnosis of substance dependence;
- Proficiency in Mandarin language;
- Failure to detox more than three times;
- Long-term methadone maintenance treatment;
- Capacity to provide informed consent (understanding of the study purpose and methods);
Exclusion Criteria:
- Schizophrenia(MINI diagnosis);
- Antisocial personality disorder(MINI diagnosis);
- Contraindications of a MRI-examination, e.g. implanted cardiac pacemaker/heart defibrillator;
- Severe cognitive impairments(MoCA ≤ 22);
- Enrollment in other clinical trials;
- Stereotactic respectively neurosurgical intervention in the past;
- Contraindications of stereotactic intervention, e.g. increased bleeding disposition, cerebrovascular diseases (e.g. arteriovenous malfunction, aneurysms, systemic vascular diseases);
- Serious or instable organic diseases (e.g. instable coronal heart disease);
- Tested positively for HIV;
- Pregnancy and/or lactation;
- Epilepsy or other severe brain trauma or neurological impairments;
Contacts and Locations
Locations
| China, Shanghai | |
| Shanghai Ruijin Hospital Functional Neurosurgery | Recruiting |
| Shanghai, Shanghai, China, 200025 | |
| Contact: Chencheng Zhang, MD +086-18217122884 i@cczhang.org | |
| Contact: Yingying Zhang, MSc +086-17602137369 zhyy019@126.com | |
Sponsors and Collaborators
Ruijin Hospital
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 14, 2019 | ||||
| First Posted Date ICMJE | May 16, 2019 | ||||
| Last Update Posted Date | January 10, 2020 | ||||
| Actual Study Start Date ICMJE | May 13, 2019 | ||||
| Estimated Primary Completion Date | June 1, 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Changes in Methadone dose [ Time Frame: Baseline (preoperative),1 month, 3 months,6 months,9 months, 12 months ] The volume of daily methadone the patients used.
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures |
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| Original Other Pre-specified Outcome Measures | Same as current | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment | ||||
| Official Title ICMJE | Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment | ||||
| Brief Summary |
Methadone maintenance treatment (MMT) is one of the main forms of treatments for opioid dependence. Despite its effectiveness and widespread use, people will experience withdrawal if daily dose is insufficient or missed, promoting reluctance to attempt detoxification. In addition, methadone is a full opioid agonist which can induce respiratory depression or sedation without ceiling level, so overdose usage can be fatal. Hence, an alternative therapy is needed to completely reduce the carving for drugs and to relieve the negative affective sate caused by withdrawal. Deep brain stimulation (DBS) is a reasonable treatment approach for addiction. Since 2009 the first case report emerged, the nucleus accumbens (NAc) is still the only brain target to be investigated in clinical case series of DBS for alcohol and heroin addiction. This research will mainly investigate the effectiveness and safety of NAc-DBS for patients with methadone maintenance treatment. The investigators will also explore the influence of NAc-DBS on brain activity and cognition. |
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| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Not Applicable | ||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE | Addiction Opiate | ||||
| Intervention ICMJE | Procedure: Bilateral surgical implantation of DBS system to Nucleus Accumbens
We plan to use the SceneRay 1242 (SceneRay, SuZhou, China) electrode with a diameter of 1.27 mm and 4 contacts. The SceneRay 1242 electrode combined with the SceneRay 1181 implantable pulse generator has the advantage of adaptive coverage area for the Ventral Capsule/Ventral Striatum, enabling simultaneous implantation in the nucleus accumbens (NAc; 2 ventral contacts) and the anterior limb of the internal capsule (ALIC; 2 dorsal contacts) with independently programmed parameters such as frequency, amplitude, and voltage; and remote and wireless programing, which allows for convenient and prompt adjustments in emergency situations. The contact length is 3.0 mm and the spacings between the ventral and dorsal contacts are 2 mm, 4 mm, and 4 mm, respectively, spanning a total length of 22.5 mm (3 + 2 + 3 + 4 + 3 + 4 + 3 mm, with 0.5 mm projecting from the electrode tip).
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| Study Arms ICMJE | Experimental: DBS
All subjects will undergo bilateral surgical implantation of DBS system in the Nucleus Accumbens. The DBS system will be active at two days after surgery.
Intervention: Procedure: Bilateral surgical implantation of DBS system to Nucleus Accumbens
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| Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Unknown status | ||||
| Estimated Enrollment ICMJE |
12 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | June 1, 2021 | ||||
| Estimated Primary Completion Date | June 1, 2021 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 65 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | China | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03952455 | ||||
| Other Study ID Numbers ICMJE | 2019 NAc-DBS MMT | ||||
| Has Data Monitoring Committee | Not Provided | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | Bomin Sun, Ruijin Hospital | ||||
| Study Sponsor ICMJE | Ruijin Hospital | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE | Not Provided | ||||
| PRS Account | Ruijin Hospital | ||||
| Verification Date | May 2019 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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