FibromyalgiaPhase 1NCT00294281
Vagus Nerve Stimulation for Treating Adults With Severe Fibromyalgia
A Phase 1 study testing Vagus Nerve Stimulation (VNS) Therapy in people with Fibromyalgia, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.
Trial summary
Fibromyalgia syndrome (FMS) is a long-term disorder that is characterized by widespread body pain and tender points in joints, muscles, tendons, and other soft tissues. Other symptoms associated with the disorder include fatigue and depression. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Vagus Nerve Stimulation (VNS) Therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Jun 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of FMS for at least 2 years, as according to the 1990 guidelines of the American College of Rheumatology (ACR) criteria. In addition, ruling out of any other medical illness to which pain may be attributed.
- Inadequate relief in FMS pain despite good treatment efforts using standard pharmacological pain management. Only patients who are work-disabled because of FMS pain are eligible for study participation if they are on opioid maintenance therapy.
- Overall FMS pain at an intensity of 5 or greater on a 0-10 verbally anchored pain intensity scale, on more than 50% of days over a consecutive 7-day period before study entry
- Has not changed pharmacological and/or non-pharmacological (e.g., yoga, exercise) treatment regimen for the 4 weeks before the first study visit and continues to experience severe pain
- At least average premorbid IQ, as assessed by the vocabulary subtest of the WAIS-III, which is a standardized, well-validated index of premorbid intellectual function
- Willing to use an acceptable method of birth control
- Able to comply with all testing and follow-up visit requirements defined by the study protocol
- Currently lives within a 2-hour driving commute to the study site
Who cannot join
- Rheumatologic condition other than FMS
- Secondary FMS, in which FMS is comorbid with another rheumatologic condition
- Reports that FMS pain began after a physical trauma
- In litigation that is associated with FMS condition at study entry
- Severe lifetime or current diagnosis of psychotic depression, bipolar disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders or has a clear history of other psychiatric illness before the onset of FMS
- Diagnosed with major depressive disorder and has attempted to commit suicide in the past or has active suicidal ideation
Show all 23Show fewer
- Lifetime or current history of dependence or abuse of pain medication or alcohol
- Treatment with an antipsychotic drug within 3 months of study entry
- Demonstrated a known placebo response in a previous study
- Treatment with botulinum toxin or local steroid injection for FMS within 2 months of study entry
- History of myocardial infarction or cardiac arrest
- Received general anesthesia within 30 days of implantation surgery
- Treatment with an investigational drug within a clearance duration of five times the half-life of the investigational drug or within 4 weeks of study entry
- Currently using another investigational device or drug
- Significant heart or lung condition currently under treatment and resulting in an American Society of Anesthesiologists (ASA) score greater than III
- Unilateral or bilateral cervical vagotomy
- Demand cardiac pacemaker, implantable defibrillator, or other implantable stimulator
- Any of the following conditions if over the age of 50 years old: cardiac conductance abnormalities, Wolf-Parkinson-White Syndrome, surgical intervention for bradycardia, history of prolonged QT interval, or a history of syncopal or pre-syncopal episodes
- Likely to require a whole body MRI after VNS system implantation
- Currently receiving or likely to receive after implantation short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy
- Plans to relocate or move to a location distant from the study site within 1 year of study entry
- Previously enrolled in this or any other VNS system study
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, 07107
About this study
Official title: A Pilot Study to Assess the Tolerability and Exploratory Efficacy of Vagus Nerve Stimulation (VNS) Using the VNS Therapy System in Patients With Refractory Fibromyalgia With and Without Major Depression
Fibromyalgia syndrome (FMS) is a long-term disorder that is characterized by widespread body pain and tender points in joints, muscles, tendons, and other soft tissues. Other symptoms associated with the disorder include fatigue and depression. The cause of FMS is unknown, and conventional treatments are often unsuccessful in adequately relieving pain. For people with severe, unrelenting pain, which is referred to as refractory FMS, opioid maintenance therapy may be an option, but it comes with the dangerous potential of addiction and is therefore avoided if possible. Vagus nerve stimulation (VNS), in which a nerve located in the neck receives electrical input, may be an option for providing pain relief. The purpose of this study is to determine the safety, tolerability, and effectiveness of VNS as a treatment for people with refractory FMS.
Read the detailed description
FMS affects about 5% of the general population and occurs most often in women between the ages of 20 and 50 years old. Overall, more than 80% of FMS patients report that pain is the primary symptom that limits their ability to work, about 30% of patients are disabled, and about 45% collect Social Security Disability insurance. Conventional treatments, which include pharmacological and behavioral interventions, fail to provide adequate pain relief in more than half of FMS patients, strongly suggesting the need for improved treatment options.
One such option is a treatment called vagus nerve stimulation (VNS), in which short bursts of electrical energy are directed into the brain by way of the vagus nerve. The vagus nerve is a cranial nerve that originates in the brainstem, travels through the neck, and then continues down through the thorax and abdomen. The nerve acts as both a sensory and motor nerve, and it can regulate several brain areas involved in pain and emotional processing. With VNS, a small battery device is surgically implanted under the skin, usually under the chest, and provides the necessary electrical energy for stimulation. Although VNS has been FDA approved for some forms of epilepsy and depression, it has yet to receive FDA approval for FMS. Also, it is unknown whether the safety and tolerability profile of an FMS patient receiving VNS is the same as that of a patient with epilepsy or depression who is receiving VNS. The purpose of this study is to determine the safety, tolerability, and effectiveness of VNS as a treatment option for adults with refractory FMS.
Participants will be in this study for about 25 months. An initial screening period that may last up to 6 weeks will include a medical history review, various examinations, and the use of a wrist-mounted device called an Actiwatch to record pain severity and mood over seven consecutive days. Eligible participants will then undergo surgical implantation of the VNS system. This will be followed by a 2-week recovery period, then a 2-week period of gradually increasing the electrical output of the VNS system, and finally a 12-week VNS treatment period during which the electrical output level will remain constant, unless a participant develops intolerable side effects. Study visits will occur weekly for the first month after implantation and then every 2 weeks during the treatment period. During most study visits, participants will undergo a clinical assessment, including evaluation of any side effects, and they will complete written assessments on pain, mood, fatigue, and quality of life and sleep. The VNS system will also be checked for safety and programmed appropriately. During the Week 16 visit, some of the screening evaluations will be repeated. Also at Week 16, which will mark the end of the treatment period, participants will have the option to continue receiving treatment. All participants will have follow-up evaluations at Months 6, 9, 12, and 24. Participants who wish to retain the VNS implantation beyond the length of the study will be referred to a qualified neurologist for follow-up care. For the other participants, the VNS system will be turned off and surgically explanted.
- Conditions
- Fibromyalgia
- Being tested
- Vagus Nerve Stimulation (VNS) Therapy
- Keywords
- Pain, Tenderness, Depression, Work Disability, Physical Function, Quality of Life, Chronic Pain
- Medical subject headings
- Fibromyalgia, Pain, Depression, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagus Nerve Stimulation (VNS) TherapyDevice
The VNS Therapy System Pulse Generator is an implantable, multi-programmable bipolar pulse generator. The pulse generator will deliver electrical signals to the vagus nerve via bipolar leads. A programming wand and software system enable non-invasive programming, functional assessments, interrogation, and data retrieval.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will undergo surgical implantation of the VNS system. This will be followed by a 2-week recovery period, then a 2-week period of gradually increasing the electrical output of the VNS system, and finally a 12-week VNS treatment period during which the electrical output level will remain constant. Follow-up will occur until Month 24. Receives: Device: Vagus Nerve Stimulation (VNS) Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: Measured at Week 16, which is the acute study exit
Secondary outcomes (4)
FM 20 multidimensional response index (FM 20)
Measured: Measured at Week 16, which is the acute study exit
Assessment of pain intensity
Measured: Measured at Week 16, which is the acute study exit
Assessment of function
Measured: Measured at Week 16, which is the acute study exit
Assessment of patient global perception
Measured: Measured at Week 16, which is the acute study exit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2006 (estimated)
- Study startOct 2006
- Primary completionMay 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Medicine and Dentistry of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Neurological Disorders and Stroke (NINDS)
- Investigators
- Gudrun Lange, PhD, Principal investigator, University of Medicine and Dentistry of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00294281
- Sponsor's protocol ID
- R01AR053732
- Other IDs
- 5R01AR053732, FM-01
- Status last verified
- Jul 2010
- First submitted
- 16 Feb 2006
- Last updated
- 20 Sep 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lange G, Janal MN, Maniker A, Fitzgibbons J, Fobler M, Cook D, Natelson BH. Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med. 2011 Sep;12(9):1406-13. doi: 10.1111/j.1526-4637.2011.01203.x. Epub 2011 Aug 3.
PubMed 21812908
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Tolerability and Exploratory Efficacy of Vagus Nerve Stimulation (VNS) Using the VNS Therapy System in Patients With Refractory Fibromyalgia With and Without Major Depression
- ClinicalTrials.gov ID
- NCT00294281
- Acronym / sponsor ID
- R01AR053732
- Conditions
- Fibromyalgia
- Keywords
- Pain, Tenderness, Depression, Work Disability, Physical Function, Quality of Life, Chronic Pain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Medicine and Dentistry of New JerseyUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Oct 2006
- Primary completion
- May 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 20 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fibromyalgia syndrome (FMS) is a long-term disorder that is characterized by widespread body pain and tender points in joints, muscles, tendons, and other soft tissues. Other symptoms associated with the disorder include fatigue and depression. The cause of FMS is unknown, and conventional treatments are often unsuccessful in adequately relieving pain. For people with severe, unrelenting pain, which is referred to as refractory FMS, opioid maintenance therapy may be an option, but it comes with the dangerous potential of addiction and is therefore avoided if possible. Vagus nerve stimulation (VNS), in which a nerve located in the neck receives electrical input, may be an option for providing pain relief. The purpose of this study is to determine the safety, tolerability, and effectiveness of VNS as a treatment for people with refractory FMS.
Detailed description
FMS affects about 5% of the general population and occurs most often in women between the ages of 20 and 50 years old. Overall, more than 80% of FMS patients report that pain is the primary symptom that limits their ability to work, about 30% of patients are disabled, and about 45% collect Social Security Disability insurance. Conventional treatments, which include pharmacological and behavioral interventions, fail to provide adequate pain relief in more than half of FMS patients, strongly suggesting the need for improved treatment options.
One such option is a treatment called vagus nerve stimulation (VNS), in which short bursts of electrical energy are directed into the brain by way of the vagus nerve. The vagus nerve is a cranial nerve that originates in the brainstem, travels through the neck, and then continues down through the thorax and abdomen. The nerve acts as both a sensory and motor nerve, and it can regulate several brain areas involved in pain and emotional processing. With VNS, a small battery device is surgically implanted under the skin, usually under the chest, and provides the necessary electrical energy for stimulation. Although VNS has been FDA approved for some forms of epilepsy and depression, it has yet to receive FDA approval for FMS. Also, it is unknown whether the safety and tolerability profile of an FMS patient receiving VNS is the same as that of a patient with epilepsy or depression who is receiving VNS. The purpose of this study is to determine the safety, tolerability, and effectiveness of VNS as a treatment option for adults with refractory FMS.
Participants will be in this study for about 25 months. An initial screening period that may last up to 6 weeks will include a medical history review, various examinations, and the use of a wrist-mounted device called an Actiwatch to record pain severity and mood over seven consecutive days. Eligible participants will then undergo surgical implantation of the VNS system. This will be followed by a 2-week recovery period, then a 2-week period of gradually increasing the electrical output of the VNS system, and finally a 12-week VNS treatment period during which the electrical output level will remain constant, unless a participant develops intolerable side effects. Study visits will occur weekly for the first month after implantation and then every 2 weeks during the treatment period. During most study visits, participants will undergo a clinical assessment, including evaluation of any side effects, and they will complete written assessments on pain, mood, fatigue, and quality of life and sleep. The VNS system will also be checked for safety and programmed appropriately. During the Week 16 visit, some of the screening evaluations will be repeated. Also at Week 16, which will mark the end of the treatment period, participants will have the option to continue receiving treatment. All participants will have follow-up evaluations at Months 6, 9, 12, and 24. Participants who wish to retain the VNS implantation beyond the length of the study will be referred to a qualified neurologist for follow-up care. For the other participants, the VNS system will be turned off and surgically explanted.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Device: Vagus Nerve Stimulation (VNS) TherapyParticipants will undergo surgical implantation of the VNS system. This will be followed by a 2-week recovery period, then a 2-week period of gradually increasing the electrical output of the VNS system, and finally a 12-week VNS treatment period during which the electrical output level will remain constant. Follow-up will occur until Month 24. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Diagnosis of FMS for at least 2 years, as according to the 1990 guidelines of the American College of Rheumatology (ACR) criteria. In addition, ruling out of any other medical illness to which pain may be attributed.
- Inadequate relief in FMS pain despite good treatment efforts using standard pharmacological pain management. Only patients who are work-disabled because of FMS pain are eligible for study participation if they are on opioid maintenance therapy.
- Overall FMS pain at an intensity of 5 or greater on a 0-10 verbally anchored pain intensity scale, on more than 50% of days over a consecutive 7-day period before study entry
- Has not changed pharmacological and/or non-pharmacological (e.g., yoga, exercise) treatment regimen for the 4 weeks before the first study visit and continues to experience severe pain
- At least average premorbid IQ, as assessed by the vocabulary subtest of the WAIS-III, which is a standardized, well-validated index of premorbid intellectual function
Key exclusion criteria (23 listed)
- Rheumatologic condition other than FMS
- Secondary FMS, in which FMS is comorbid with another rheumatologic condition
- Reports that FMS pain began after a physical trauma
- In litigation that is associated with FMS condition at study entry
- Severe lifetime or current diagnosis of psychotic depression, bipolar disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders or has a clear history of other psychiatric illness before the onset of FMS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vagus Nerve Stimulation (VNS) TherapyThe VNS Therapy System Pulse Generator is an implantable, multi-programmable bipolar pulse generator. The pulse generator will deliver electrical signals to the vagus nerve via bipolar leads. A programming wand and software system enable non-invasive programming, functional assessments, interrogation, and data retrieval. | Device | 1 |
Primary outcome
Incidence of adverse events
Time frame: Measured at Week 16, which is the acute study exit
4 secondary outcomes
FM 20 multidimensional response index (FM 20)
Time frame: Measured at Week 16, which is the acute study exit
Assessment of pain intensity
Time frame: Measured at Week 16, which is the acute study exit
Assessment of function
Time frame: Measured at Week 16, which is the acute study exit
Assessment of patient global perception
Time frame: Measured at Week 16, which is the acute study exit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2011.
- Derived from this study: PubMed 21812908Lange G, Janal MN, Maniker A, Fitzgibbons J, Fobler M, Cook D, Natelson BH. Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med. 2011 Sep;12(9):1406-13. doi: 10.1111/j.1526-4637.2011.01203.x. Epub 2011 Aug 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gudrun Lange, PhD principal investigator
University of Medicine and Dentistry of New Jersey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vagus Nerve Stimulation (VNS) Therapy in people with Fibromyalgia, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Measured at Week 16, which is the acute study exit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00294281, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2011.