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Neuromodulation in Patients With Painful Chronic Pancreatitis

Primary Purpose

Painful Chronic Pancreatitis, Visceral Pain, Neuropathic Pain

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
GammaCore Device
Sham Device
Sponsored by
Jens Brøndum Frøkjær
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Painful Chronic Pancreatitis focused on measuring Chronic pancreatitis, Vagal nerve stimulation, Visceral Pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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.

Sites / Locations

  • Mech-Sense, Department of Radiology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Gammacore Device

Sham Device

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Change in quality of life QoLQ
Changes in pain and physical functioning composite scores of the modified brief pain inventory-short form (mBPI-sf).
Patient Global Impression of Change (PGIC).
Quantitative sensory testing (thermal, mechanical and muscle stimulation, including conditioned pain modulation)
Cardiac vagal tone
Blood samples
Changes in cytokines will be assessed .

Full Information

First Posted
November 21, 2017
Last Updated
February 15, 2022
Sponsor
Jens Brøndum Frøkjær
Collaborators
ElectroCore INC
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1. Study Identification

Unique Protocol Identification Number
NCT03357029
Brief Title
Neuromodulation in Patients With Painful Chronic Pancreatitis
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 11, 2018 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
April 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jens Brøndum Frøkjær
Collaborators
ElectroCore INC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Chronic Pancreatitis, Visceral Pain, Neuropathic Pain
Keywords
Chronic pancreatitis, Vagal nerve stimulation, Visceral Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gammacore Device
Arm Type
Active Comparator
Arm Description
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
Arm Title
Sham Device
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
GammaCore Device
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham Device
Intervention Description
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.
Primary Outcome Measure Information:
Title
The perceived clinical pain measured by pain diary based on Visual Analog Scale (VAS)
Description
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.
Time Frame
Up to 8 weeks.
Title
Detection of brain changes using magnetic resonance imaging (MRI)
Description
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.
Time Frame
Up to 8 weeks.
Secondary Outcome Measure Information:
Title
Change in quality of life QoLQ
Time Frame
Up to 8 weeks.
Title
Changes in pain and physical functioning composite scores of the modified brief pain inventory-short form (mBPI-sf).
Time Frame
Up to 8 weeks.
Title
Patient Global Impression of Change (PGIC).
Time Frame
Up to 8 weeks.
Title
Quantitative sensory testing (thermal, mechanical and muscle stimulation, including conditioned pain modulation)
Time Frame
Up to 8 weeks.
Title
Cardiac vagal tone
Time Frame
Up to 8 weeks.
Title
Blood samples
Description
Changes in cytokines will be assessed .
Time Frame
Up to 8 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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.
Facility Information:
Facility Name
Mech-Sense, Department of Radiology
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
33635894
Citation
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.
Results Reference
derived
PubMed Identifier
31603076
Citation
Muthulingam 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.
Results Reference
derived

Learn more about this trial

Neuromodulation in Patients With Painful Chronic Pancreatitis

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