Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment

Addiction Opiate Clinical Trial

Official title:

Deep Brain Stimulation of the Bilateral Nucleus Accumbens for Patients With Methadone Maintenance Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03952455
• Other study ID #: 2019 NAc-DBS MMT
• Status: Recruiting
• Phase: N/A
• Start date: May 13, 2019
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2019
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• Addiction Opiate
• Behavior, Addictive

Intervention

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).

Locations

Country	Name	City	State
China	Shanghai Ruijin Hospital Functional Neurosurgery	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Kuhn J, Möller M, Treppmann JF, Bartsch C, Lenartz D, Gruendler TO, Maarouf M, Brosig A, Barnikol UB, Klosterkötter J, Sturm V. Deep brain stimulation of the nucleus accumbens and its usefulness in severe opioid addiction. Mol Psychiatry. 2014 Feb;19(2):145-6. doi: 10.1038/mp.2012.196. Epub 2013 Jan 22. — View Citation

Müller UJ, Sturm V, Voges J, Heinze HJ, Galazky I, Büntjen L, Heldmann M, Frodl T, Steiner J, Bogerts B. Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial. Pharmacopsychiatry. 2016 Jul;49(4):170-3. doi: 10.1055/s-0042-104507. Epub 2016 May 4. — View Citation

Müller UJ, Voges J, Steiner J, Galazky I, Heinze HJ, Möller M, Pisapia J, Halpern C, Caplan A, Bogerts B, Kuhn J. Deep brain stimulation of the nucleus accumbens for the treatment of addiction. Ann N Y Acad Sci. 2013 Apr;1282:119-28. doi: 10.1111/j.1749-6632.2012.06834.x. Epub 2012 Dec 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Barratt impulsiveness scale	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.	Baseline(preoperative)
Other	UPPS-P impulsive behavior scale	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.	Baseline(preoperative)
Primary	Changes in Methadone dose	The volume of daily methadone the patients used.	Baseline (preoperative),1 month, 3 months,6 months,9 months, 12 months
Secondary	Hamilton Depression Scale(HAMD-17)	17 items, Total scores<7: normal; 7	Baseline(preoperative),1 month, 3 months, 6 months, 9 months, 12 months
Secondary	Hamilton Anxiety Scale (HAMA)	14 items, Total scores<6: normal; 7	Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months
Secondary	Young Manic Rating Scale (YMRS)	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.	Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months
Secondary	Monitoring of Side Effects Scale (MOSES)	To evaluate side effects. The higher score means more severity of side effects.	Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months
Secondary	Changes in Subjective Opiate Withdrawal Scale(SOWS)	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).	Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months
Secondary	Obsessive compulsive drug use scale(OCDUS)	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.	Baseline(preoperative),1 month, 3 months, 6 months,9 months, 12 months
Secondary	The MOS item short from health survey (SF-36)	36 items. To evaluate the quality of life and the higher score indicates better quality of life.	Baseline(preoperative),1 month, 3 months,6 months,9 months, 12 months
Secondary	World Health Organization Quality of Life-BREF (WHO-BREF)	26 items. The higher score means the better quality of life.	Baseline(preoperative),1 month, 3 months,6 months,9 months, 12 months
Secondary	Fagerstrom Test for Nicotine Dependence assessment (FTND)	To evaluate Nicotine Dependence. The higher of scores indicates higher level of Nicotine Dependence	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Beck depression inventory(BDI)	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.	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Beck anxiety inventory(BAI)	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.	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Perceived stress scale(PSS-10)	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.	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Twenty Item Positive and Negative Affect Schedule (PANAS)	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).	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Work and Social Adjustment Scale(WSAS)	Self-rated scale. The maximum score of the WSAS is 40, lower scores are better.	Baseline(preoperative),1 month, 3months,6months,9 months, 12 months
Secondary	Cognitive performance	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.	Baseline(preoperative),6 months,12 months
Secondary	Brain activity	PET(Positron Emission Tomography) or fMRI(functional Magnetic Resonance Imaging) are used in this study.	Baseline(preoperative), 6 months,12 months