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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

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

NCT ID

NCT03357029

First Posted

November 21, 2017

Last Updated

February 15, 2022

Sponsor

Jens Brøndum Frøkjær

Collaborators

ElectroCore INC

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

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

Arm Title

Sham Device

Arm Type

Sham Comparator

Arm Description

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

Time Frame

Up to 8 weeks.

Title

Detection of brain changes using magnetic resonance imaging (MRI)

Description

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

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

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Neuromodulation in Patients With Painful Chronic Pancreatitis

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