Herpes ZosterNCT07399288
Postherpetic Neuralgia After Herpes Zoster and Incident Dementia Risk
An observational study of Herpes Zoster and Dementia, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
This retrospective observational cohort study uses de-identified electronic health record data from the TriNetX Global Collaborative Network to evaluate whether postherpetic neuralgia after herpes zoster is associated with an increased risk of incident dementia. Read more about this study
- Who is it for?
- Ages 40 to 120 years
- Conditions the study is for
- Herpes Zoster, Dementia, Postherpetic Neuralgia (PHN)
- What is being tested?
- Exposure: postherpetic neuralgia
- How many people
- 73,404 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Oct 2015to 29 Oct 2026
- 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 40 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population comprises adults aged 40 to 120 years with incident herpes zoster identified in the TriNetX Global Collaborative Network from 1 October 2015 to 31 December 2024. Exposure groups are defined by the presence or absence of recorded postherpetic neuralgia diagnoses within 90 to 365 days after the index herpes zoster date. Follow-up for outcomes starts at a 365-day landmark after index among individuals alive and free of the outcome at the landmark. Replication analyses are performed in the TriNetX Asia Pacific (APAC) network.
Who may be able to join
- Adults aged 40 to 120 years with an incident herpes zoster diagnosis recorded between 1 October 2015 and 31 December 2024 in the TriNetX network.
- A 3-year washout period with no recorded herpes zoster diagnosis before the index date.
- Eligible for analysis at the 365-day landmark after the index date, defined as being alive and free of the specified outcome at the landmark.
Who cannot join
- Any record of the specified outcome before the 365-day landmark.
- Missing data elements required to define exposure status within the prespecified time window.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Postherpetic Neuralgia After Herpes Zoster and Risk of Incident Dementia: Real-World Evidence From an International Matched Cohort With Landmark Analysis
This retrospective observational cohort study uses de-identified electronic health record data from the TriNetX Global Collaborative Network to evaluate whether postherpetic neuralgia after herpes zoster is associated with an increased risk of incident dementia. Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 are identified using diagnostic codes. Postherpetic neuralgia is defined by International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes B02.22 or B02.29 recorded between 90 and 365 days after the index herpes zoster date, and comparators have no such codes between 90 and 365 days after index. The primary analysis uses 1:1 propensity score matching and a 365-day landmark design, including only individuals alive and free of dementia at the landmark. Time-to-event analyses estimate hazard ratios for incident dementia and related outcomes.
Read the detailed description
Data source and study design This is a retrospective cohort study using de-identified electronic health record data accessed through the TriNetX platform. The primary analysis is conducted in the TriNetX Global Collaborative Network. Replication is performed in the TriNetX Asia Pacific (APAC) network as a geographic validation.
Population and index date Eligible individuals are aged 40 to 120 years and have an incident herpes zoster diagnosis (ICD-10-CM B02) recorded between 1 October 2015 and 31 December 2024, with a 3-year washout period free of herpes zoster before the index date. Baseline covariates are assessed up to 1 day before the index date.
Exposure definition Postherpetic neuralgia is defined by ICD-10-CM codes B02.22 or B02.29 recorded between 90 and 365 days after the index date. The comparator cohort includes individuals with incident herpes zoster and no record of B02.22 or B02.29 between 90 and 365 days after the index date. A prespecified stricter exposure definition requires at least two postherpetic neuralgia codes separated by at least 30 days.
Landmark design and follow-up The primary analysis uses a 365-day landmark after the index date. Only individuals alive and free of the specified outcome at the landmark enter the risk set. Follow-up starts at the landmark and continues until the first record of the outcome, death, or the last recorded fact in the patient's record, up to the date of data extraction.
Matching and analysis Cohorts are matched 1:1 using nearest neighbour propensity score matching with a caliper of 0.1. Balance is assessed using standardised mean differences. Time-to-event analyses use Kaplan-Meier methods and Cox proportional hazards models, reporting hazard ratios with 95% confidence intervals.
Outcomes The primary outcome is incident all-cause dementia defined by ICD-10-CM codes F01, F02, F03, or G30. Prespecified secondary outcomes include Alzheimer disease, vascular dementia, other or unspecified dementia, all-cause mortality, ischaemic stroke, and hip fracture. The Benjamini-Hochberg false discovery rate is applied to the six secondary outcomes only. A negative control outcome of acute appendicitis (ICD-10-CM K35) is included to assess residual bias.
Sensitivity and validation analyses Prespecified analyses include an alternative 730-day landmark, the stricter postherpetic neuralgia definition, additional adjustment for recorded zoster vaccination as a baseline covariate, and replication in the TriNetX APAC network using prespecified matching settings.
- Conditions
- Herpes Zoster, Dementia, Postherpetic Neuralgia (PHN)
- Being tested
- Exposure: postherpetic neuralgia
- Keywords
- Landmark analysis, Propensity score matching, TriNetX, Alzheimer disease, Vascular dementia, Zoster vaccination, Negative control outcome
- Medical subject headings
- Herpes Zoster, Dementia, Neuralgia, Postherpetic, Alzheimer Disease, Dementia, Vascular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure: postherpetic neuralgiaOther
This is an observational study and no treatment is assigned by the investigators. The intervention of interest is exposure status defined by recorded diagnoses of postherpetic neuralgia after herpes zoster, based on ICD-10-CM codes B02.22 or B02.29 within 90 to 365 days after the index herpes zoster date.
| Study group | Role | What they receive |
|---|---|---|
| Postherpetic neuralgia (PHN) | Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 who had a recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) between 90 and 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark. Receives: Other: Exposure: postherpetic neuralgia | |
| Non-PHN comparator | Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 with no recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) between 90 and 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incident all-cause dementia
Incident all-cause dementia is identified using ICD-10-CM codes F01, F02, F03, or G30. Individuals with any record of dementia before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of dementia, death or the last recorded fact, up to the date of data extraction.
Secondary outcomes (6)
Alzheimer disease
Incident Alzheimer disease is identified using ICD-10-CM code G30. Individuals with any record of Alzheimer disease before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of Alzheimer disease, death or the last recorded fact, up to the date of data extraction.
Vascular dementia
Incident vascular dementia is identified using ICD-10-CM code F01. Individuals with any record of vascular dementia before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of vascular dementia, death or the last recorded fact, up to the date of data extraction.
Other or unspecified dementia
Incident other or unspecified dementia is identified using ICD-10-CM codes F02 or F03. Individuals with any record of these diagnoses before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of other or unspecified dementia, death or the last recorded fact, up to the date of data extraction.
All-cause mortality
All-cause mortality is identified using the death indicator available within the TriNetX network.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of death or the last recorded fact, up to the date of data extraction.
Ischaemic stroke
Incident ischaemic stroke is identified using ICD-10-CM code I63. Individuals with any record of ischaemic stroke before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of ischaemic stroke, death or the last recorded fact, up to the date of data extraction.
Hip fracture
Incident hip fracture is identified using ICD-10-CM codes S72.0, S72.1, or S72.2. Individuals with any record of hip fracture before the 365-day landmark are excluded from the risk set.
Measured: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of hip fracture, death or the last recorded fact, up to the date of data extraction.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2026
- Study start1 Oct 2015
- Primary completion29 Oct 2026
- Study completion29 Oct 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Herpes ZosterStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 73,404 participants (actual)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- En-Bo Wu, MD, Principal investigator, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07399288
- Sponsor's protocol ID
- CMUH114-REC3-226
- Status last verified
- Oct 2026
- First submitted
- 3 Feb 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) cannot be shared publicly because the TriNetX data are available only to subscribing organisations under licence agreements and governance controls. Investigators access de-identified records within the platform and are not permitted to download or redistribute line-level data. Researchers with access to TriNetX can reproduce the analysis using the cohort definitions and query parameters reported in the study.
Publications
Stein E, Huser M, Amirian ES, Palchuk MB, Brown JS. TriNetX Dataworks-USA: Overview of a Multi-Purpose, De-Identified, Federated Electronic Health Record Real-World Data and Analytics Network and Comparison to the US Census. Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70198. doi: 10.1002/pds.70198.
PubMed 40915660Warren-Gash C, Williamson E, Shiekh SI, Borjas-Howard J, Pearce N, Breuer JM, Smeeth L. No evidence that herpes zoster is associated with increased risk of dementia diagnosis. Ann Clin Transl Neurol. 2022 Mar;9(3):363-374. doi: 10.1002/acn3.51525. Epub 2022 Feb 16.
PubMed 35170873Forbes HJ, Thomas SL, Smeeth L, Clayton T, Farmer R, Bhaskaran K, Langan SM. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain. 2016 Jan;157(1):30-54. doi: 10.1097/j.pain.0000000000000307.
PubMed 26218719
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postherpetic Neuralgia After Herpes Zoster and Risk of Incident Dementia: Real-World Evidence From an International Matched Cohort With Landmark Analysis
- ClinicalTrials.gov ID
- NCT07399288
- Acronym / sponsor ID
- CMUH114-REC3-226
- Conditions
- Herpes Zoster, Dementia, Postherpetic Neuralgia (PHN)
- Keywords
- Landmark analysis, Propensity score matching, TriNetX, Alzheimer disease, Vascular dementia, Zoster vaccination, Negative control outcome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 73,404 participants (actual)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 29 Oct 2026 (actual)
- Study completion
- 29 Oct 2026 (actual)
- First posted
- 10 Feb 2026 (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.
This retrospective observational cohort study uses de-identified electronic health record data from the TriNetX Global Collaborative Network to evaluate whether postherpetic neuralgia after herpes zoster is associated with an increased risk of incident dementia. Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 are identified using diagnostic codes. Postherpetic neuralgia is defined by International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes B02.22 or B02.29 recorded between 90 and 365 days after the index herpes zoster date, and comparators have no such codes between 90 and 365 days after index. The primary analysis uses 1:1 propensity score matching and a 365-day landmark design, including only individuals alive and free of dementia at the landmark. Time-to-event analyses estimate hazard ratios for incident dementia and related outcomes.
Detailed description
Data source and study design This is a retrospective cohort study using de-identified electronic health record data accessed through the TriNetX platform. The primary analysis is conducted in the TriNetX Global Collaborative Network. Replication is performed in the TriNetX Asia Pacific (APAC) network as a geographic validation.
Population and index date Eligible individuals are aged 40 to 120 years and have an incident herpes zoster diagnosis (ICD-10-CM B02) recorded between 1 October 2015 and 31 December 2024, with a 3-year washout period free of herpes zoster before the index date. Baseline covariates are assessed up to 1 day before the index date.
Exposure definition Postherpetic neuralgia is defined by ICD-10-CM codes B02.22 or B02.29 recorded between 90 and 365 days after the index date. The comparator cohort includes individuals with incident herpes zoster and no record of B02.22 or B02.29 between 90 and 365 days after the index date. A prespecified stricter exposure definition requires at least two postherpetic neuralgia codes separated by at least 30 days.
Landmark design and follow-up The primary analysis uses a 365-day landmark after the index date. Only individuals alive and free of the specified outcome at the landmark enter the risk set. Follow-up starts at the landmark and continues until the first record of the outcome, death, or the last recorded fact in the patient's record, up to the date of data extraction.
Matching and analysis Cohorts are matched 1:1 using nearest neighbour propensity score matching with a caliper of 0.1. Balance is assessed using standardised mean differences. Time-to-event analyses use Kaplan-Meier methods and Cox proportional hazards models, reporting hazard ratios with 95% confidence intervals.
Outcomes The primary outcome is incident all-cause dementia defined by ICD-10-CM codes F01, F02, F03, or G30. Prespecified secondary outcomes include Alzheimer disease, vascular dementia, other or unspecified dementia, all-cause mortality, ischaemic stroke, and hip fracture. The Benjamini-Hochberg false discovery rate is applied to the six secondary outcomes only. A negative control outcome of acute appendicitis (ICD-10-CM K35) is included to assess residual bias.
Sensitivity and validation analyses Prespecified analyses include an alternative 730-day landmark, the stricter postherpetic neuralgia definition, additional adjustment for recorded zoster vaccination as a baseline covariate, and replication in the TriNetX APAC network using prespecified matching settings.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Postherpetic neuralgia (PHN) | – | Other: Exposure: postherpetic neuralgiaAdults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 who had a recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) between 90 and 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark. |
| Non-PHN comparator | – | –Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 with no recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) between 90 and 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark. |
Who may qualify
- Ages
- 40 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population comprises adults aged 40 to 120 years with incident herpes zoster identified in the TriNetX Global Collaborative Network from 1 October 2015 to 31 December 2024. Exposure groups are defined by the presence or absence of recorded postherpetic neuralgia diagnoses within 90 to 365 days after the index herpes zoster date. Follow-up for outcomes starts at a 365-day landmark after index among individuals alive and free of the outcome at the landmark. Replication analyses are performed in the TriNetX Asia Pacific (APAC) network.
Key inclusion criteria (3 listed)
- Adults aged 40 to 120 years with an incident herpes zoster diagnosis recorded between 1 October 2015 and 31 December 2024 in the TriNetX network.
- A 3-year washout period with no recorded herpes zoster diagnosis before the index date.
- Eligible for analysis at the 365-day landmark after the index date, defined as being alive and free of the specified outcome at the landmark.
Key exclusion criteria (2 listed)
- Any record of the specified outcome before the 365-day landmark.
- Missing data elements required to define exposure status within the prespecified time window.
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 |
|---|---|---|
| Exposure: postherpetic neuralgiaThis is an observational study and no treatment is assigned by the investigators. The intervention of interest is exposure status defined by recorded diagnoses of postherpetic neuralgia after herpes zoster, based on ICD-10-CM codes B02.22 or B02.29 within 90 to 365 days after the index herpes zoster date. | Other | Postherpetic neuralgia (PHN) |
Primary outcome
Incident all-cause dementia
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of dementia, death or the last recorded fact, up to the date of data extraction.
Incident all-cause dementia is identified using ICD-10-CM codes F01, F02, F03, or G30. Individuals with any record of dementia before the 365-day landmark are excluded from the risk set.
6 secondary outcomes
Alzheimer disease
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of Alzheimer disease, death or the last recorded fact, up to the date of data extraction.
Vascular dementia
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of vascular dementia, death or the last recorded fact, up to the date of data extraction.
Other or unspecified dementia
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of other or unspecified dementia, death or the last recorded fact, up to the date of data extraction.
All-cause mortality
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of death or the last recorded fact, up to the date of data extraction.
Ischaemic stroke
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of ischaemic stroke, death or the last recorded fact, up to the date of data extraction.
Hip fracture
Time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of hip fracture, death or the last recorded fact, up to the date of data extraction.
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 2 Nov 2026.
- Background: PubMed 40915660Stein E, Huser M, Amirian ES, Palchuk MB, Brown JS. TriNetX Dataworks-USA: Overview of a Multi-Purpose, De-Identified, Federated Electronic Health Record Real-World Data and Analytics Network and Comparison to the US Census. Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70198. doi: 10.1002/pds.70198.
- Background: PubMed 35170873Warren-Gash C, Williamson E, Shiekh SI, Borjas-Howard J, Pearce N, Breuer JM, Smeeth L. No evidence that herpes zoster is associated with increased risk of dementia diagnosis. Ann Clin Transl Neurol. 2022 Mar;9(3):363-374. doi: 10.1002/acn3.51525. Epub 2022 Feb 16.
- Background: PubMed 26218719Forbes HJ, Thomas SL, Smeeth L, Clayton T, Farmer R, Bhaskaran K, Langan SM. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain. 2016 Jan;157(1):30-54. doi: 10.1097/j.pain.0000000000000307.
- TriNetX: Real-world data for the life sciences and healthcareLink provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data (IPD) cannot be shared publicly because the TriNetX data are available only to subscribing organisations under licence agreements and governance controls. Investigators access de-identified records within the platform and are not permitted to download or redistribute line-level data. Researchers with access to TriNetX can reproduce the analysis using the cohort definitions and query parameters reported in the study.
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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.
En-Bo Wu, MD principal investigator
China Medical University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Herpes Zoster and Dementia, run by China Medical University Hospital at 1 site in Taiwan.
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 3 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 2 Nov 2026. 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 Taiwan. 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. 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?
Incident all-cause dementia (time frame: From the 365-day landmark after the index herpes zoster date to the earliest of the first record of dementia, death or the last recorded fact, up to the date of data extraction.). 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 NCT07399288, which also lists 3 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 2 Nov 2026.