Postherpetic NeuralgiaNCT03106896
Involvement of Reorganization of Cerebral Functional Connectivity in the Process of Transition to Postherpetic Neuralgia
An observational study of Postherpetic Neuralgia, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
Trial summary
Postherpetic neuralgia(PHN) is a chronic neuropathic pain syndrome which persists more than 3 months after the resolution of the acute shingles episode. PHN is a complicated neuropathic pain that results from the sustained peripheral injury by herpes zoster and its pathological mechanism in skin and spine has been… Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Postherpetic Neuralgia
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- Apr 2017to Jun 2020
- Phase
- Observational
- 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 50 to 80 years
- All sexes
- Adult, Older adult
Study population: The PHN sample size is determined according to the published reports. The AHP sample size is determined according to the 20.6% incidence of patients who translate from AHP to PHN and the drop-out rate, generally speaking, about 10%. Finally, we determine we need 54 AHP subjects, 10 PHN subjects, 11 age and gender-matched control subjects.
Who may be able to join
- All participants are more than 50 years old, right-handed. Patients are definitely diagnosed by a clinician for postherpetic neuralgia (PHN), persisting pain more than 3 months after the resolution of the acute shingles episode and have pain intensity greater than 4 on the visual analog scale (VAS 0, no pain; 10, "worst pain imaginable"). Patients who are diagnosed as acute herpes zoster at the initial interview have pain (VAS≧4 ) duration of within 7 days after zoster onset. Data are available for healthy control subjects with age and sex matched.
Who cannot join
- Subjects are excluded if they are suffering from eyes, ears, viscera, meninx herpes zoster and asymptomatic special herpes zoster. Those who report any other acute and chronic painful conditions, systemic disease, history of head injury, psychiatric diseases, or more than mild depression [(score > 19, according to Beck's Depression Inventory (BDI)] are also excluded. Subjects are excluded if they were found abnormal signal when scanning by fMRI and exist MRI contraindication, such as existence of magnetic metal in body, claustrophobia and so on. Patients who don't withdraw the analgesic medication (oxycodone, NSAIDS, gabapentin, etc.) the day before and on the day of examination are also excluded.
About this study
Postherpetic neuralgia(PHN) is a chronic neuropathic pain syndrome which persists more than 3 months after the resolution of the acute shingles episode. PHN is a complicated neuropathic pain that results from the sustained peripheral injury by herpes zoster and its pathological mechanism in skin and spine has been reported. But the cerebral mechanism is still unclear. Based on the previous study that has proved the reorganization of cerebral functional connectivity in pain chronicity, the investigators hypothesize that the process from acute herpetic pain (AHP) to PHN is also accompanied with the reorganization of functional connectivity.In the study, the investigators intend to use 7 Tesla functional magnetic resonance imaging(fMRI) to observe the difference of brain activity and functional connectivity between acute herpetic pain and PHN. Meanwhile, the investigators examine the evolution of functional connectivity longitudinally in patients who is suffering from acute pain, so as to explore the central mechanism of transition to PHN.
Read the detailed description
Postherpetic neuralgia(PHN) is a chronic neuropathic pain syndrome which persists more than 3 months after the resolution of the acute shingles episode. PHN is the most common complication of herpes zoster in the pain clinic and it was reported that 2%-35% patients who suffer from herpes zoster may continue to suffer from PHN. Along with the coming of aging population, advanced age is one of the risk factors and about 20.6% patients aged 50 years and over may translate into PHN from acute herpes zoster . Besides, the proportion may increase with age which not only seriously impacts the quality of patients' life but also causes huge personal and social healthcare burden.
PHN is a complicated neuropathic pain that results from the sustained peripheral injury by herpes zoster and its pathological mechanism in skin and spine has been reported. But the cerebral mechanism is still unclear. In the recent several years, fMRI is widely used in the cerebral mechanism in several diseases due to its no trauma and accurate positioning about brain regions. The existing fMRI research about PHN discovered that the alteration of brain activity and reorganization of cerebral functional connectivity in PHN compared with healthy subjects. Liu,et al. investigated the effects of PHN on resting-state brain activity utilizing arterial spin labeling (ASL) techniques and found that regional cerebral blood flow in left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and meanwhile, the four brain regions exist functional connectivity with other regions in different degrees. Liang,et al. explored the difference of cerebral activity between acute herpes zoster and PHN and found PHN showed higher regional homogeneity in bilateral thalamus, right cerebellum, right hippocampus, right fusiform gyrus, right insula. They speculated tha the thalamus, cerebellum, insula may be associated with hyperalgesia and hippocampus may be associated with pain memory in PHN patients.
In conclusion, fMRI showed that insula, thalamus, hippocampus, striatum and so on are connected with PHN. And then the investigators are curious about the cerebral alteration before the patient is definitely diagnosed as PHN. Meanwhile it's commonly presented in clinic that why some patients who suffer from herpes zoster can heal without PHN while someone are suffering from PHN in a long time. The investigators assume that cerebral alteration and its functional connectivity are associated with the transition to PHN. That is to say, it's a study of mechanism about the transition from acute herpes zoster pain to PHN. Some studies have shown that the reorganization of neural network, especially the function connectivity between cortex and limbic system, is involved in the transition to chronic back pain and affects the sense, emotion, cognition, movement of pain. Apkarian ,et al. used fMRI to identify intrinsic and extrinsic hippocampal functional connectivity, comparing subacute back pain (SBP, back pain 1-4 mo) and chronic back pain (CBP, back pain﹥1 yr) patients to control subjects. Both groups showed more extensive hippocampal connectivity than CON subjects. They then examined the evolution of hippocampal connectivity longitudinally in SBP patients who recovered (SBPr, back pain decreased﹥20% in 1 yr) and those with persistent pain (SBPp) and found that SBPp and SBPr subjects have distinct changes in hippocampal-cortical connectivity over 1 yr. Specifically, SBPp subjects showed large decreases in hippocampal connectivity with medial prefrontal cortex. These results demonstrated that the reorganization of hippocampal functional connectivity is associated with the transition to chronic back pain. They also found that nucleus accumbens(NAc)-medial prefrontal cortex(mPFC) functional connectivity is also involved in the transition to chronic back pain.
So the investigators hypothesize that the process from acute herpetic pain (AHP) to PHN is also accompanied with the reorganization of functional connectivity.
With the development of technology, 7 Tesla fMRI is coming into our sight. Andreas, et al. showed that 7 Tesla-fMRI with the increased field strength offers marked improvement for the localization of activation foci with high spatial specificity when comparing neural response to painful electrical stimulation with 3 Tesla. In our study, the investigators intend to use 7 Tesla fMRI to observe the difference of brain activity and functional connectivity between acute herpetic pain and PHN. Meanwhile, the investigators examine the evolution of functional connectivity longitudinally in patients who is suffering from acute pain, so as to explore the central mechanism of transition to PHN.
- Conditions
- Postherpetic Neuralgia
- Medical subject headings
- Neuralgia, Postherpetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| postherpetic neuralgia (PHN group) | persist more than 3 months after the resolution of the acute shingles episode and have pain intensity greater than 4 on the visual analog scale (VAS 0, no pain; 10, "worst pain imaginable"). | |
| acute herpetic pain (AHP group) | have pain (VAS≧4 ) duration of within 7 days after zoster onset at initial interview | |
| healthy control (CON group) | healthy population |
What is being measured
The primary outcome is the main question the study is designed to answer.
functional connectivity between several brain regions
The functional connectivity between several brain regions in AHP group and PHN group is different. Besides, the reorganization of cerebral functional connectivity in the process of transition to postherpetic neuralgia is relevant with the chronicity of symptom.
Measured: AHPand CON subjects are scanned at four visits over the course of six months to observe the variation trend of connectivity from the AHP to PHN. PHN group need only one scanning.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2017
- Study startApr 2017 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postherpetic NeuralgiaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03106896
- Sponsor's protocol ID
- 2016-069
- Status last verified
- Dec 2016
- First submitted
- 26 Mar 2017
- Last updated
- 11 Apr 2017
- Results posted
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Involvement of Reorganization of Cerebral Functional Connectivity in the Process of Transition to Postherpetic Neuralgia
- ClinicalTrials.gov ID
- NCT03106896
- Acronym / sponsor ID
- 2016-069
- Conditions
- Postherpetic Neuralgia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- Apr 2017 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 11 Apr 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.
Postherpetic neuralgia(PHN) is a chronic neuropathic pain syndrome which persists more than 3 months after the resolution of the acute shingles episode. PHN is a complicated neuropathic pain that results from the sustained peripheral injury by herpes zoster and its pathological mechanism in skin and spine has been reported. But the cerebral mechanism is still unclear. Based on the previous study that has proved the reorganization of cerebral functional connectivity in pain chronicity, the investigators hypothesize that the process from acute herpetic pain (AHP) to PHN is also accompanied with the reorganization of functional connectivity.In the study, the investigators intend to use 7 Tesla functional magnetic resonance imaging(fMRI) to observe the difference of brain activity and functional connectivity between acute herpetic pain and PHN. Meanwhile, the investigators examine the evolution of functional connectivity longitudinally in patients who is suffering from acute pain, so as to explore the central mechanism of transition to PHN.
Detailed description
Postherpetic neuralgia(PHN) is a chronic neuropathic pain syndrome which persists more than 3 months after the resolution of the acute shingles episode. PHN is the most common complication of herpes zoster in the pain clinic and it was reported that 2%-35% patients who suffer from herpes zoster may continue to suffer from PHN. Along with the coming of aging population, advanced age is one of the risk factors and about 20.6% patients aged 50 years and over may translate into PHN from acute herpes zoster . Besides, the proportion may increase with age which not only seriously impacts the quality of patients' life but also causes huge personal and social healthcare burden.
PHN is a complicated neuropathic pain that results from the sustained peripheral injury by herpes zoster and its pathological mechanism in skin and spine has been reported. But the cerebral mechanism is still unclear. In the recent several years, fMRI is widely used in the cerebral mechanism in several diseases due to its no trauma and accurate positioning about brain regions. The existing fMRI research about PHN discovered that the alteration of brain activity and reorganization of cerebral functional connectivity in PHN compared with healthy subjects. Liu,et al. investigated the effects of PHN on resting-state brain activity utilizing arterial spin labeling (ASL) techniques and found that regional cerebral blood flow in left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and meanwhile, the four brain regions exist functional connectivity with other regions in different degrees. Liang,et al. explored the difference of cerebral activity between acute herpes zoster and PHN and found PHN showed higher regional homogeneity in bilateral thalamus, right cerebellum, right hippocampus, right fusiform gyrus, right insula. They speculated tha the thalamus, cerebellum, insula may be associated with hyperalgesia and hippocampus may be associated with pain memory in PHN patients.
In conclusion, fMRI showed that insula, thalamus, hippocampus, striatum and so on are connected with PHN. And then the investigators are curious about the cerebral alteration before the patient is definitely diagnosed as PHN. Meanwhile it's commonly presented in clinic that why some patients who suffer from herpes zoster can heal without PHN while someone are suffering from PHN in a long time. The investigators assume that cerebral alteration and its functional connectivity are associated with the transition to PHN. That is to say, it's a study of mechanism about the transition from acute herpes zoster pain to PHN. Some studies have shown that the reorganization of neural network, especially the function connectivity between cortex and limbic system, is involved in the transition to chronic back pain and affects the sense, emotion, cognition, movement of pain. Apkarian ,et al. used fMRI to identify intrinsic and extrinsic hippocampal functional connectivity, comparing subacute back pain (SBP, back pain 1-4 mo) and chronic back pain (CBP, back pain﹥1 yr) patients to control subjects. Both groups showed more extensive hippocampal connectivity than CON subjects. They then examined the evolution of hippocampal connectivity longitudinally in SBP patients who recovered (SBPr, back pain decreased﹥20% in 1 yr) and those with persistent pain (SBPp) and found that SBPp and SBPr subjects have distinct changes in hippocampal-cortical connectivity over 1 yr. Specifically, SBPp subjects showed large decreases in hippocampal connectivity with medial prefrontal cortex. These results demonstrated that the reorganization of hippocampal functional connectivity is associated with the transition to chronic back pain. They also found that nucleus accumbens(NAc)-medial prefrontal cortex(mPFC) functional connectivity is also involved in the transition to chronic back pain.
So the investigators hypothesize that the process from acute herpetic pain (AHP) to PHN is also accompanied with the reorganization of functional connectivity.
With the development of technology, 7 Tesla fMRI is coming into our sight. Andreas, et al. showed that 7 Tesla-fMRI with the increased field strength offers marked improvement for the localization of activation foci with high spatial specificity when comparing neural response to painful electrical stimulation with 3 Tesla. In our study, the investigators intend to use 7 Tesla fMRI to observe the difference of brain activity and functional connectivity between acute herpetic pain and PHN. Meanwhile, the investigators examine the evolution of functional connectivity longitudinally in patients who is suffering from acute pain, so as to explore the central mechanism of transition to PHN.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| postherpetic neuralgia (PHN group) | – | –persist more than 3 months after the resolution of the acute shingles episode and have pain intensity greater than 4 on the visual analog scale (VAS 0, no pain; 10, "worst pain imaginable"). |
| acute herpetic pain (AHP group) | – | –have pain (VAS≧4 ) duration of within 7 days after zoster onset at initial interview |
| healthy control (CON group) | – | –healthy population |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The PHN sample size is determined according to the published reports. The AHP sample size is determined according to the 20.6% incidence of patients who translate from AHP to PHN and the drop-out rate, generally speaking, about 10%. Finally, we determine we need 54 AHP subjects, 10 PHN subjects, 11 age and gender-matched control subjects.
Key inclusion criteria (1 listed)
- All participants are more than 50 years old, right-handed. Patients are definitely diagnosed by a clinician for postherpetic neuralgia (PHN), persisting pain more than 3 months after the resolution of the acute shingles episode and have pain intensity greater than 4 on the visual analog scale (VAS 0, no pain; 10, "worst pain imaginable"). Patients who are diagnosed as acute herpes zoster at the initial interview have pain (VAS≧4 ) duration of within 7 days after zoster onset. Data are available for healthy control subjects with age and sex matched.
Key exclusion criteria (1 listed)
- Subjects are excluded if they are suffering from eyes, ears, viscera, meninx herpes zoster and asymptomatic special herpes zoster. Those who report any other acute and chronic painful conditions, systemic disease, history of head injury, psychiatric diseases, or more than mild depression [(score > 19, according to Beck's Depression Inventory (BDI)] are also excluded. Subjects are excluded if they were found abnormal signal when scanning by fMRI and exist MRI contraindication, such as existence of magnetic metal in body, claustrophobia and so on. Patients who don't withdraw the analgesic medication (oxycodone, NSAIDS, gabapentin, etc.) the day before and on the day of examination are also excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
functional connectivity between several brain regions
Time frame: AHPand CON subjects are scanned at four visits over the course of six months to observe the variation trend of connectivity from the AHP to PHN. PHN group need only one scanning.
The functional connectivity between several brain regions in AHP group and PHN group is different. Besides, the reorganization of cerebral functional connectivity in the process of transition to postherpetic neuralgia is relevant with the chronicity of symptom.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Postherpetic Neuralgia, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Results are not available in the source record.
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?
functional connectivity between several brain regions (time frame: AHPand CON subjects are scanned at four visits over the course of six months to observe the variation trend of connectivity from the AHP to PHN. PHN group need only one scanning.). 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 11 Apr 2017.