Painful Chronic PancreatitisNCT03357029
Neuromodulation in Patients With Painful Chronic Pancreatitis
A study testing GammaCore Device in people with Painful Chronic Pancreatitis and Visceral Pain, run by Jens Brøndum Frøkjær at 1 site in Denmark.
Trial summary
The purpose of this trial is to explore if a novel vagal neuromodulation approach provides analgesic benefit through central mechanisms in patients with chronic pancreatitis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Painful Chronic Pancreatitis, Visceral Pain, Neuropathic Pain
- What is being tested?
- GammaCore Device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteDenmark
- Study dates
- 11 Jan 2018to 30 Apr 2019
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients from the ages of 18 with a diagnosis of CP diagnosed using the Mayo Clinic diagnostic criteria.
- The participants must be able to read and understand Danish.
- The patients must suffer from chronic abdominal pain characteristic for CP, meet the criteria for chronic pain (pain ≥ 3 days per week in at least 3 months) and must consider their pain as insufficiently treated with their usual analgesic treatment.
- Personally, signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial as well as signing the following document: "Informeret samtykke om opbevaring af biologisk material i biobank til fremtidig forskning".
- Personally, signed and dated the Power of attorney document (Fuldmagtserklæring) indicating that the patient has accepted that the Danish Medical Agency Sundhedsstyrelsen/Lægemiddelstyrelen) have access to the medical records.
- Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures.
Who cannot join
- Patients with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
- Alcohol dependence (Alcohol use in accordance with the recommendations by the Danish Health and Medicines Authority are allowed).
- Illegal drug dependencies.
- Participating in another study where investigational drug is used.
- Patients must not suffer from painful conditions other than CP that make them unable to distinguish the pain associated with CP from chronic pain of other origin.
- Cardiovascular diseases
Show all 19Show fewer
- Low blood pressure < 100/60
- Not able to understand or follow the instructions.
- Any condition with elevated intracranial pressure.
- Female patients who are pregnant or lactating, or intend to become pregnant and male patients who intend to father a child during the course of the study. A pregnancy test will be conducted at baseline and after 8 weeks to ensure that female patients are not pregnant during the study medication period. The investigator will have to urge that fertile female patients use a safe contraception method during the study and for at least 15 hours after termination of the study medication period. The following methods are considered as safe contraception methods:
- The combined oral contraceptive pill
- Intra uterine device
- Gestagen injection
- Subdermal implantation
- Hormone vaginal ring
- Transdermal plaster
- Contraindications for MRI: Such as metallic Foreign Body in the Eye, "Triggerfish" Contact Lens, Gastric Reflux Device, Insulin Pumps, Permanent pacemaker, Temporary external transvenous pacing leads, Other implantable metallic components which is considered unsafe by the medical doctor.
- Previous surgery on vagus nerve.
- Known neuropathy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuromodulation in Patients With Painful Chronic Pancreatitis - A Randomized, Double-blind, Sham-controlled, Prospective, Cross-over, Controlled Study in Chronic Pain Investigating if a Novel Vagal Neuromodulation Approach Provides Analgesic Benefit Through Central Mechanisms in Patients With Chronic Pancreatitis
The purpose of this trial is to explore if a novel vagal neuromodulation approach provides analgesic benefit through central mechanisms in patients with chronic pancreatitis
Read the detailed description
This study is a randomized, double blind, sham-controlled, cross-over, controlled investigation. The overall objective of the study is to conduct a study of vagal tone and the sensory system (brain activity, sensory testing, and questionnaires) assessing the effect of two weeks' transcutaneous vagal neuromodulation in chronic pancreatitis patients not responding adequately to traditional pharmacological pain treatment, in comparison to the effect of two weeks' sham treatment. The active treatment will be performed using a commercially available and validated device called GammaCore (the active treatment) while the sham treatment will be performed using a sham-device. GammaCore device is a non-invasive neurostimulator that has been approved for the treatment of anxiety, primary headache, including migraine.
The study will begin with a one-week baseline registration period, in which the patients will receive no treatment. Next, the baseline period will be followed by a 2-week treatment period where the subjects will be randomized to either active treatment or the sham treatment. Afterwards, a wash-out period of one week and a second baseline registration period of one week will occur. Finally, in the second treatment period the patients will switch in treatment assignment, meaning that patient who received active treatment in the beginning, will now receive sham treatment and vice versa. During both treatments, the patients will be asked to self-administer one stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm). During the whole study, subjects will be asked to complete a pain diary and several questionnaires. Moreover, at the beginning and end of each treatment period (four times), all subjects will undergo testing which will include magnetic resonance imaging (MRI), quantitative sensory testing (QST), cardiac vagal tone (CVT) and collecting blood samples.
The primary efficacy parameters to be evaluated are clinical pain relief and brain alterations using MRI.
- Being tested
- GammaCore Device, Sham Device
- Keywords
- Chronic pancreatitis, Vagal nerve stimulation, Visceral Pain
- Medical subject headings
- Visceral Pain, Neuralgia, Pancreatitis, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GammaCore DeviceDevice
GammaCore will be administered using a handheld device the size of a mobile phone, which consists of a battery powered portable stimulator with a digital control user interface that controls the stimulation amplitude and two steel contact electrodes.
Sham DeviceDevice
Sham device will be administered using a handheld device the size of a mobile phone, which consists of a battery powered portable stimulator with a digital control user interface that controls the stimulation amplitude and two steel contact electrodes. The sham device is identical in appearance, weight, visual and audible feedback, and user application and control but did not deliver electrical stimulations.
| Study group | Role | What they receive |
|---|---|---|
| Gammacore Device | Active comparator | The GammaCore Device is a non-Invasive vagus nerve stimulator. One stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm) for two weeks Receives: Device: GammaCore Device |
| Sham Device | Sham comparator | The Sham GammaCore device looks and operates like the Active GammaCore device, but does not deliver a therapeutic stimulation treatment.
One stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm) for two weeks. Receives: Device: Sham Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
The perceived clinical pain measured by pain diary based on Visual Analog Scale (VAS)
The primary clinical efficacy parameter to be evaluated is pain relief. In the clinical part of the study the efficacy is assessed as changes in the daily experience of pain, which will be measured using a patient pain diary based on the visual analog scale (VAS). Maximum intensity and average daily VAS will be recorded on daily basis.
Measured: Up to 8 weeks.
Detection of brain changes using magnetic resonance imaging (MRI)
The primary experimental endpoint is detection of structural, functional, metabolic brain alterations using MRI techniques in order to study the brain mechanisms involved in chronic pain and central sensitization.
Measured: Up to 8 weeks.
Secondary outcomes (6)
Change in quality of life QoLQ
Measured: Up to 8 weeks.
Changes in pain and physical functioning composite scores of the modified brief pain inventory-short form (mBPI-sf).
Measured: Up to 8 weeks.
Patient Global Impression of Change (PGIC).
Measured: Up to 8 weeks.
Quantitative sensory testing (thermal, mechanical and muscle stimulation, including conditioned pain modulation)
Measured: Up to 8 weeks.
Cardiac vagal tone
Measured: Up to 8 weeks.
Blood samples
Changes in cytokines will be assessed .
Measured: Up to 8 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2017
- Study start11 Jan 2018
- Primary completion30 Apr 2019
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Painful Chronic PancreatitisStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jens Brøndum Frøkjær
- Sponsor type
- University, hospital or other
- Collaborators
- ElectroCore INC
- Responsible party
- Sponsor-investigator, Jens Brøndum Frøkjær, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03357029
- Sponsor's protocol ID
- VNS project
- Status last verified
- Feb 2022
- First submitted
- 21 Nov 2017
- Last updated
- 17 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Muthulingam JA, Olesen SS, Hansen TM, Brock C, Drewes AM, Frokjaer JB. Cervical transcutaneous vagal neuromodulation in chronic pancreatitis patients with chronic pain: A randomised sham controlled clinical trial. PLoS One. 2021 Feb 26;16(2):e0247653. doi: 10.1371/journal.pone.0247653. eCollection 2021.
PubMed 33635894Muthulingam JA, Olesen SS, Hansen TM, Brock C, Drewes AM, Frokjaer JB. Study protocol for a randomised double-blinded, sham-controlled, prospective, cross-over clinical trial of vagal neuromodulation for pain treatment in patients with chronic pancreatitis. BMJ Open. 2019 Aug 23;9(7):e029546. doi: 10.1136/bmjopen-2019-029546.
PubMed 31603076
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation in Patients With Painful Chronic Pancreatitis - A Randomized, Double-blind, Sham-controlled, Prospective, Cross-over, Controlled Study in Chronic Pain Investigating if a Novel Vagal Neuromodulation Approach Provides Analgesic Benefit Through Central Mechanisms in Patients With Chronic Pancreatitis
- ClinicalTrials.gov ID
- NCT03357029
- Acronym / sponsor ID
- VNS project
- Keywords
- Chronic pancreatitis, Vagal nerve stimulation, Visceral Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Jens Brøndum FrøkjærUniversity, hospital or other
- Collaborators
- ElectroCore INC
- Study start
- 11 Jan 2018 (actual)
- Primary completion
- 30 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 29 Nov 2017 (actual)
- 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.
The purpose of this trial is to explore if a novel vagal neuromodulation approach provides analgesic benefit through central mechanisms in patients with chronic pancreatitis
Detailed description
This study is a randomized, double blind, sham-controlled, cross-over, controlled investigation. The overall objective of the study is to conduct a study of vagal tone and the sensory system (brain activity, sensory testing, and questionnaires) assessing the effect of two weeks' transcutaneous vagal neuromodulation in chronic pancreatitis patients not responding adequately to traditional pharmacological pain treatment, in comparison to the effect of two weeks' sham treatment. The active treatment will be performed using a commercially available and validated device called GammaCore (the active treatment) while the sham treatment will be performed using a sham-device. GammaCore device is a non-invasive neurostimulator that has been approved for the treatment of anxiety, primary headache, including migraine.
The study will begin with a one-week baseline registration period, in which the patients will receive no treatment. Next, the baseline period will be followed by a 2-week treatment period where the subjects will be randomized to either active treatment or the sham treatment. Afterwards, a wash-out period of one week and a second baseline registration period of one week will occur. Finally, in the second treatment period the patients will switch in treatment assignment, meaning that patient who received active treatment in the beginning, will now receive sham treatment and vice versa. During both treatments, the patients will be asked to self-administer one stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm). During the whole study, subjects will be asked to complete a pain diary and several questionnaires. Moreover, at the beginning and end of each treatment period (four times), all subjects will undergo testing which will include magnetic resonance imaging (MRI), quantitative sensory testing (QST), cardiac vagal tone (CVT) and collecting blood samples.
The primary efficacy parameters to be evaluated are clinical pain relief and brain alterations using MRI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gammacore Device | Active comparator | Device: GammaCore DeviceThe GammaCore Device is a non-Invasive vagus nerve stimulator. One stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm) for two weeks |
| Sham Device | Sham comparator | Device: Sham DeviceThe Sham GammaCore device looks and operates like the Active GammaCore device, but does not deliver a therapeutic stimulation treatment. One stimulation dose bilaterally to the cervical vagal neck area, three times per day (morning 8 am., afternoon 2 pm, and evening 8 pm) for two weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients from the ages of 18 with a diagnosis of CP diagnosed using the Mayo Clinic diagnostic criteria.
- The participants must be able to read and understand Danish.
- The patients must suffer from chronic abdominal pain characteristic for CP, meet the criteria for chronic pain (pain ≥ 3 days per week in at least 3 months) and must consider their pain as insufficiently treated with their usual analgesic treatment.
- Personally, signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial as well as signing the following document: "Informeret samtykke om opbevaring af biologisk material i biobank til fremtidig forskning".
- Personally, signed and dated the Power of attorney document (Fuldmagtserklæring) indicating that the patient has accepted that the Danish Medical Agency Sundhedsstyrelsen/Lægemiddelstyrelen) have access to the medical records.
Key exclusion criteria (19 listed)
- Patients with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
- Alcohol dependence (Alcohol use in accordance with the recommendations by the Danish Health and Medicines Authority are allowed).
- Illegal drug dependencies.
- Participating in another study where investigational drug is used.
- Patients must not suffer from painful conditions other than CP that make them unable to distinguish the pain associated with CP from chronic pain of other origin.
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 |
|---|---|---|
| GammaCore DeviceGammaCore will be administered using a handheld device the size of a mobile phone, which consists of a battery powered portable stimulator with a digital control user interface that controls the stimulation amplitude and two steel contact electrodes. | Device | Gammacore Device |
| Sham DeviceSham device will be administered using a handheld device the size of a mobile phone, which consists of a battery powered portable stimulator with a digital control user interface that controls the stimulation amplitude and two steel contact electrodes. The sham device is identical in appearance, weight, visual and audible feedback, and user application and control but did not deliver electrical stimulations. | Device | Sham Device |
Primary outcome
The perceived clinical pain measured by pain diary based on Visual Analog Scale (VAS)
Time frame: Up to 8 weeks.
The primary clinical efficacy parameter to be evaluated is pain relief. In the clinical part of the study the efficacy is assessed as changes in the daily experience of pain, which will be measured using a patient pain diary based on the visual analog scale (VAS). Maximum intensity and average daily VAS will be recorded on daily basis.
Detection of brain changes using magnetic resonance imaging (MRI)
Time frame: Up to 8 weeks.
The primary experimental endpoint is detection of structural, functional, metabolic brain alterations using MRI techniques in order to study the brain mechanisms involved in chronic pain and central sensitization.
6 secondary outcomes
Change in quality of life QoLQ
Time frame: Up to 8 weeks.
Changes in pain and physical functioning composite scores of the modified brief pain inventory-short form (mBPI-sf).
Time frame: Up to 8 weeks.
Patient Global Impression of Change (PGIC).
Time frame: Up to 8 weeks.
Quantitative sensory testing (thermal, mechanical and muscle stimulation, including conditioned pain modulation)
Time frame: Up to 8 weeks.
Cardiac vagal tone
Time frame: Up to 8 weeks.
Blood samples
Time frame: Up to 8 weeks.
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 17 Feb 2022.
- Derived from this study: PubMed 33635894Muthulingam JA, Olesen SS, Hansen TM, Brock C, Drewes AM, Frokjaer JB. Cervical transcutaneous vagal neuromodulation in chronic pancreatitis patients with chronic pain: A randomised sham controlled clinical trial. PLoS One. 2021 Feb 26;16(2):e0247653. doi: 10.1371/journal.pone.0247653. eCollection 2021.
- Derived from this study: PubMed 31603076Muthulingam JA, Olesen SS, Hansen TM, Brock C, Drewes AM, Frokjaer JB. Study protocol for a randomised double-blinded, sham-controlled, prospective, cross-over clinical trial of vagal neuromodulation for pain treatment in patients with chronic pancreatitis. BMJ Open. 2019 Aug 23;9(7):e029546. doi: 10.1136/bmjopen-2019-029546.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GammaCore Device in people with Painful Chronic Pancreatitis and Visceral Pain, run by Jens Brøndum Frøkjær at 1 site in Denmark.
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 6 inclusion and 19 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 17 Feb 2022. 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 Denmark. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
The perceived clinical pain measured by pain diary based on Visual Analog Scale (VAS) (time frame: Up to 8 weeks.). The study lists 2 primary outcomes in all. 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 NCT03357029, which also lists 2 linked publications.
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 17 Feb 2022.