Safety Study of Deep Brain Stimulation to Manage Thalamic Pain Syndrome

NCT01072656 | Completed Results DMC

• 2 other identifiers: AGM-0011DP2OD006469-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and efficacy of Deep Brian Stimulation (DBS) of the ventral capsular/ventral striatal as a treatment for patients with Thalamic Pain Syndrome (TPS). The central hypothesis to be tested in this investigation is that VC/VS stimulation will modulate the affective component of TPS and, consequently, improve pain related disability.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 50% Improvement in Pain Related Disability (as Assessed by the Pain Disability Index)

  Pain Disability Index (PDI) directly measures disability related to the main components of daily life function and has been validated for thalamic pain syndrome. Range is 0 (no disability) to 10 (worst disability). The components are Family/Home Responsibilities, Recreation, Social Activity, Sexual Behavior, Life-support Activity, Occupation, \& Self-care. This is an average score of the 3 month period for each Active and Sham phase.

  Blinded stimulation phase (3 Months)

Secondary Outcomes (3)

• Number of Participants Who Had 50% Improvement in PDI

  24 months post randomization follow up

• Number of Participants Who Would Undergo the Procedure Again.

  End of Open Label Phase (24 months)

• Number of Patient Who Had >50% Reduction in VAS.

  Baseline and 24 months

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

Active stimulation and programmed to the settings found to be optimal during the titration process.

Device: Deep Brain Stimulation for Thalamic Pain Syndrome

Control group

SHAM COMPARATOR

IPG is set to ON but the voltage is set to 0V.

Device: Deep Brain Stimulation for Thalamic Pain Syndrome

Interventions

Deep Brain Stimulation for Thalamic Pain Syndrome DEVICE

Patients will be randomized in a 1:1 ratio to one of two groups: the Treatment Group (active stimulation and programmed to the settings found to be optimal during the titration phase) and the Control Group (sham stimulation - IPG is set to ON but the voltage is set to 0V). In order to prevent too many patients from being randomized to ON or to sham early in the study, we will use, for the first 4 patients, randomization blocks of four or six. In this fashion, the first four consecutive patients will have two patients randomized to the Treatment Group and two patients in the Control Group. In the same fashion, the final six patients will have three patients randomized to the treatment group and three patients to the control group.

Control group; Treatment group

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of thalamic pain syndrome
• with allodynia or dysesthesia
• with pinprick anesthesia or hypoesthesia on the affected hemibody (anesthesia dolorosa).
• Six months or more of medically refractory severe pain (see below).
• Pain disability reported by the pain index \>30 points at the time of enrollment.
• Average daily pain for the past 30 days reported as \>5 on a 0-10 scale
• Failure to respond adequately to at least one antidepressant, one anti-seizure medication and one oral narcotic.
• MRI done within one year of the first visit showing a lesion that involves the posterior thalamic region or a lesion in the dorsal or ventral vicinity of the thalamus (i.e. semi oval white matter or brain stem). The lesion will be contralateral to the hemibody affected by chronic pain or will involve cortical-subcortical areas in topography consistent with sensory thalamocortical connections. This will include patients with infarcts in the territory of the middle cerebral artery. A more recent MRI may be required if the patient's condition changed within the previous year.
• Capable of understanding and providing informed consent
• Age ≥ 21 years
• Women of childbearing age must be on regular use of an accepted contraceptive method(s).
• Previous surgical procedures: Patients with severe and refractory thalamic pain syndrome may have undergone other interventional or surgical procedures, as an attempt to alleviate the thalamic pain syndrome. Surgical procedure may include blocks, spinal cord stimulation, thalamic DBS, posterior limb of the internal capsule DBS or periaqueductal gray / periventricular gray DBS, cortical stimulation, peripheral ablative procedures or cerebral ablative procedures. In this study, patients with previously implanted cortical stimulation systems, or spinal and peripheral nervous system stimulation systems may be included. However, patients with previous motor cortex stimulation must have had the cortical stimulation system before being considered a candidate for this protocol. Removal of the cortical stimulation system will not be covered under this protocol. Patients with spinal or peripheral neuromodulation system may be included in the research provided that the implanted systems are compatible with the all research protocols (including fMRI) to be performed during the research. Patients with pervious DBS implants will not be considered candidates.

You may not qualify if:

• Not capable of understanding or providing informed consent.
• Aphasia severe enough to limit the consent process or communication between the investigators and the patient. Patients with mild or recovering aphasia may be considered candidates at the discretion of the PI.
• Coagulopathy. Patients will be excluded unless assessed and cleared by hematology
• Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after surgery. Patients taking these medications will need to discuss the need/risk of continuing these medications with their physicians and the PI or study personnel may contact the treating physician(s) as well to discuss the risks of anticoagulation / antiaggregation therapy discontinuation.
• Uncontrolled hypertension.
• Malignancy with \< 5 years life expectancy.
• Major medical co-morbidities: end stage renal failure, heart failure, severe congestive heart disease, severe respiratory problems, liver failure or other significant medical co morbidities.
• Major neurological disorder other than the one that led to the TPS.
• MRI (done within one year of the first visit) with abnormalities other than those associated with the neurological disorder causing TPS.
• Age \< 21 years.
• Pregnancy or lack of regular use of contraceptives. Patients who become pregnant after enrollment may be excluded from the study. Patients who become pregnant prior to the surgical implantation of the DBS systems will be excluded from the study.
• Previous ablative intracranial surgery for the management of the TPS.
• Previously implanted with deep brain stimulation system.
• Concurrent enrolment in any other trial / study for TPS.
• Implantable hardware not compatible with MRI or with the study.

Sponsors & Collaborators

• Andre Machado: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (3)

• Gopalakrishnan R, Burgess RC, Lempka SF, Gale JT, Floden DP, Machado AG. Pain anticipatory phenomena in patients with central poststroke pain: a magnetoencephalography study. J Neurophysiol. 2016 Sep 1;116(3):1387-95. doi: 10.1152/jn.00215.2016. Epub 2016 Jun 29.

  PMID: 27358316 BACKGROUND

• Gopalakrishnan R, Burgess RC, Plow EB, Floden DP, Machado AG. Early event related fields during visually evoked pain anticipation. Clin Neurophysiol. 2016 Mar;127(3):1855-63. doi: 10.1016/j.clinph.2015.11.019. Epub 2015 Dec 5.

  PMID: 26733321 BACKGROUND

• Plow EB, Malone DA Jr, Machado A. Deep brain stimulation of the ventral striatum/anterior limb of the internal capsule in thalamic pain syndrome: study protocol for a pilot randomized controlled trial. Trials. 2013 Jul 31;14:241. doi: 10.1186/1745-6215-14-241.

  PMID: 23902631 DERIVED

MeSH Terms

Conditions

Chronic Pain

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr Andre Machado
• Organization: Cleveland Clinic

machada@ccf.org

216-444-4270

Study Officials

• Andre G Machado, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: February 19, 2010
• First Posted: February 22, 2010
• Study Start: May 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: March 1, 2016
• Last Updated: June 9, 2017
• Results First Posted: August 30, 2016

Record last verified: 2017-05

Locations

US (1)