Pain, AcuteHypnoPainNCT05336370
Decoding Mechanisms of Pain Modulation
A study testing Hypnosis and Vagus nerve stimulation in people with Pain, Acute, run by University of Oslo at 1 site in Norway.
Trial summary
The main objective of this experimental trial is to gain further insights into the mechanisms of pain modulation, and more specifically, whether expectations of coping is one of the involved mechanisms. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Acute
- What is being tested?
- Hypnosis and Vagus nerve stimulation
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 1 siteNorway
- Study dates
- 1 Aug 2022to 17 Nov 2023
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults aged 18-70 years
- Fluent Norwegian language skills
Who cannot join
- History of cardiovascular disease
- Chronic pain conditions (any diagnoses resulting in chronic pain)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Decoding Mechanisms of Pain Modulation Through Hypnosis and Vagus Nerve Stimulation
The main objective of this experimental trial is to gain further insights into the mechanisms of pain modulation, and more specifically, whether expectations of coping is one of the involved mechanisms. This will be investigated by comparing two different interventions known to influence pain perception; hypnosis and non-invasive stimulation of the vagus nerve, prior to a pain exposure task (hand immersion in cold water). Expectations will be assessed both pre- and post intervention.
Read the detailed description
Pain is a subjective experience, influenced by biological, psychological and social factors. This multidimensional view of pain has led to various efforts to affect people's pain experience. Nonpharmacological interventions, such as hypnosis, have proven successful in reducing pain whilst providing few, if any, negative side effects. Hypnosis involves a state of highly focused attention, with a constriction in peripheral awareness and a heightened responsiveness to social cues. This particular state can exert a powerful influence on the mind and body, yet the mechanisms responsible for this effect remains to a large degree unknown. The aim of this study is to investigate the effect of hypnosis given prior to a painful procedure (cold pressor test, CPT), to investigate the effect on pain perception and tolerance, but most importantly, to investigate if the effect is mediated by a change in expectations of coping. Previous studies have provided support for the the effect of hypnosis on expectations, but they have focused exclusively on stimulus expectancies (expectations of pain intensity), while the current study will focus on response outcome expectancies (expectations of coping) in line with the Cognitive Activation Theory of Stress (CATS).
Whilst hypnosis may dampen the stress response through expectancies (top-down), another way of dampening the stress response is through transcutaneous vagus nerve stimulation (tVNS) (bottom-up). Vagus nerve stimulation is proposed as another nonopioid pain treatment with minimal side effects. The vagus nerve is the 10th cranial nerve, connecting the viscera and the brain and influencing multiple systems of the body including the cardiac, immunologic, and endocrine system, and the activity of many visceral organs. This makes the vagus nerve a possibly important mediating (transmitting) and modulating nerve of pain signals . Stimulation of the vagus nerve is believed to modulate pain by inhibiting inflammation, oxidative stress, and sympathetic activity, and possibly also by inducing a brain activation pattern that may be incongruent with the pain matrix (i.e. brain regions commonly active during pain). VNS might also mediate the effects of the opioid system in pain modulation. These mechanisms have in common that they are hypothesized to affect neuronal hyperexcitability, resulting in a reduced pain perception, which is supported by experimental animal studies.
- Conditions
- Pain, Acute
- Being tested
- Hypnosis, Vagus nerve stimulation, Sham control
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HypnosisBehavioural
The hypnosis will be conducted by clinical psychologists who have the formal competence and training in hypnosis. We will be using a tailored hypnosis script designed for this particular study, with a duration of 10-15 minutes. The script involves a hypnotic induction (relaxation-based), imagery (suggestions for pleasant visual imagery), a deepening procedure, and symptom-specific suggestions. The introduction begins by having the hypnotist debunk many of the common myths and misconceptions that patients may hold about hypnosis, and provide a description of hypnosis. Hypnosis is described as focused attention and concentration - like being so lost in a book or movie that it is easy to lose track of what is going on around you. Once the patient is deeply hypnotized, the therapist offers suggestions to reduce distress and improve pain tolerance.
Vagus nerve stimulationDevice
A CE approved tVNS device will be used to stimulate the afferent auricular branch of the vagus nerve located medial of the tragus at the entry of the acoustic meatus [36]. A standardized intensity of 10 mA with a pulse width of 250 μs and a consistent stimulation frequency of 25 Hz will be used for optimal stimulation. The stimulation will constantly alternate between active stimulation for 30 seconds, followed by a break of 30 seconds [37], and will have a duration of 15 minutes. Active tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing downward. The bipolar stimulation electrode is placed correctly within the concha of the left ear. Participants are instructed to breathe normally while not talking or making any movements during their session.
Sham controlDevice
Sham tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing upward. The bipolar stimulation electrode is placed correctly within the concha of the left ear, but no actual stimulation will be performed. The electrode will be left on for 15 minutes. Participants are instructed to breathe normally while not talking or making any movements during their session
| Study group | Role | What they receive |
|---|---|---|
| Hypnosis | Experimental | A brief hypnosis session will be provided to participants in this arm prior to immersion in the cold water. Receives: Behavioral: Hypnosis |
| Active tVNS | Experimental | Participants in the active tVNS condition will receive electronic stimulation of the vagus nerve prior to immersion in the cold water. Receives: Device: Vagus nerve stimulation |
| Sham tVNS | Sham comparator | Participants in the sham tVNS will receive the electrode similar to the active treatment, but no stimulation will be performed. Receives: Device: Sham control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain tolerance
Time elapsed before removing the hand from the water.
Measured: up to 10 minutes (During exposure (hand immersion in cold water))
Secondary outcomes (2)
Pain intensity
rated on a NRS 0-10 where 0 is "no pain" and 10 is "the worst pain imaginable"
Measured: Immediately after the cold pressor test
Pain bothersomeness
NRS 0-10 where 0 is "not bothersome at all" and 10 is "the most bothersome imaginable"
Measured: Immediately after the cold pressor test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start1 Aug 2022
- Primary completion17 Nov 2023
- Study completion17 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, AcuteStudies 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
- Parallel groups
- Model description
- The HypnoPain trial is designed as an experimental randomized controlled, statistician blinded superiority trial with three parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oslo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silje Endresen Reme, University of Oslo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05336370
- Sponsor's protocol ID
- 409472
- Acronym
- HypnoPain
- Status last verified
- Dec 2023
- First submitted
- 12 Apr 2022
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We plan to share the study protocol, README files as well the statistical codes for the main analysis in an open repository (e.g. Open Science Framework) to ensure transparency and reproducability.
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decoding Mechanisms of Pain Modulation Through Hypnosis and Vagus Nerve Stimulation
- ClinicalTrials.gov ID
- NCT05336370
- Acronym / sponsor ID
- HypnoPain / 409472
- Conditions
- Pain, Acute
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- University of OsloUniversity, hospital or other
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 17 Nov 2023 (actual)
- Study completion
- 17 Nov 2023 (actual)
- First posted
- 20 Apr 2022 (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 main objective of this experimental trial is to gain further insights into the mechanisms of pain modulation, and more specifically, whether expectations of coping is one of the involved mechanisms. This will be investigated by comparing two different interventions known to influence pain perception; hypnosis and non-invasive stimulation of the vagus nerve, prior to a pain exposure task (hand immersion in cold water). Expectations will be assessed both pre- and post intervention.
Detailed description
Pain is a subjective experience, influenced by biological, psychological and social factors. This multidimensional view of pain has led to various efforts to affect people's pain experience. Nonpharmacological interventions, such as hypnosis, have proven successful in reducing pain whilst providing few, if any, negative side effects. Hypnosis involves a state of highly focused attention, with a constriction in peripheral awareness and a heightened responsiveness to social cues. This particular state can exert a powerful influence on the mind and body, yet the mechanisms responsible for this effect remains to a large degree unknown. The aim of this study is to investigate the effect of hypnosis given prior to a painful procedure (cold pressor test, CPT), to investigate the effect on pain perception and tolerance, but most importantly, to investigate if the effect is mediated by a change in expectations of coping. Previous studies have provided support for the the effect of hypnosis on expectations, but they have focused exclusively on stimulus expectancies (expectations of pain intensity), while the current study will focus on response outcome expectancies (expectations of coping) in line with the Cognitive Activation Theory of Stress (CATS).
Whilst hypnosis may dampen the stress response through expectancies (top-down), another way of dampening the stress response is through transcutaneous vagus nerve stimulation (tVNS) (bottom-up). Vagus nerve stimulation is proposed as another nonopioid pain treatment with minimal side effects. The vagus nerve is the 10th cranial nerve, connecting the viscera and the brain and influencing multiple systems of the body including the cardiac, immunologic, and endocrine system, and the activity of many visceral organs. This makes the vagus nerve a possibly important mediating (transmitting) and modulating nerve of pain signals . Stimulation of the vagus nerve is believed to modulate pain by inhibiting inflammation, oxidative stress, and sympathetic activity, and possibly also by inducing a brain activation pattern that may be incongruent with the pain matrix (i.e. brain regions commonly active during pain). VNS might also mediate the effects of the opioid system in pain modulation. These mechanisms have in common that they are hypothesized to affect neuronal hyperexcitability, resulting in a reduced pain perception, which is supported by experimental animal studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- The HypnoPain trial is designed as an experimental randomized controlled, statistician blinded superiority trial with three parallel groups
| Arm | Type | Receives |
|---|---|---|
| Hypnosis | Experimental | Behavioral: HypnosisA brief hypnosis session will be provided to participants in this arm prior to immersion in the cold water. |
| Active tVNS | Experimental | Device: Vagus nerve stimulationParticipants in the active tVNS condition will receive electronic stimulation of the vagus nerve prior to immersion in the cold water. |
| Sham tVNS | Sham comparator | Device: Sham controlParticipants in the sham tVNS will receive the electrode similar to the active treatment, but no stimulation will be performed. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults aged 18-70 years
- Fluent Norwegian language skills
Key exclusion criteria (2 listed)
- History of cardiovascular disease
- Chronic pain conditions (any diagnoses resulting in chronic pain)
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 |
|---|---|---|
| HypnosisThe hypnosis will be conducted by clinical psychologists who have the formal competence and training in hypnosis. We will be using a tailored hypnosis script designed for this particular study, with a duration of 10-15 minutes. The script involves a hypnotic induction (relaxation-based), imagery (suggestions for pleasant visual imagery), a deepening procedure, and symptom-specific suggestions. The introduction begins by having the hypnotist debunk many of the common myths and misconceptions that patients may hold about hypnosis, and provide a description of hypnosis. Hypnosis is described as focused attention and concentration - like being so lost in a book or movie that it is easy to lose track of what is going on around you. Once the patient is deeply hypnotized, the therapist offers suggestions to reduce distress and improve pain tolerance. | Behavioural | Hypnosis |
| Vagus nerve stimulationA CE approved tVNS device will be used to stimulate the afferent auricular branch of the vagus nerve located medial of the tragus at the entry of the acoustic meatus [36]. A standardized intensity of 10 mA with a pulse width of 250 μs and a consistent stimulation frequency of 25 Hz will be used for optimal stimulation. The stimulation will constantly alternate between active stimulation for 30 seconds, followed by a break of 30 seconds [37], and will have a duration of 15 minutes. Active tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing downward. The bipolar stimulation electrode is placed correctly within the concha of the left ear. Participants are instructed to breathe normally while not talking or making any movements during their session. | Device | Active tVNS |
| Sham controlSham tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing upward. The bipolar stimulation electrode is placed correctly within the concha of the left ear, but no actual stimulation will be performed. The electrode will be left on for 15 minutes. Participants are instructed to breathe normally while not talking or making any movements during their session | Device | Sham tVNS |
Primary outcome
Pain tolerance
Time frame: up to 10 minutes (During exposure (hand immersion in cold water))
Time elapsed before removing the hand from the water.
2 secondary outcomes
Pain intensity
Time frame: Immediately after the cold pressor test
Pain bothersomeness
Time frame: Immediately after the cold pressor test
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 4 Dec 2023.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We plan to share the study protocol, README files as well the statistical codes for the main analysis in an open repository (e.g. Open Science Framework) to ensure transparency and reproducability.
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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 Hypnosis and Vagus nerve stimulation in people with Pain, Acute, run by University of Oslo at 1 site in Norway.
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 2 inclusion and 2 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 4 Dec 2023. 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 Norway. 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?
Pain tolerance (time frame: up to 10 minutes (During exposure (hand immersion in cold water))). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Dec 2023.