Lyme DiseaseDIALYDNCT04719962
Direct Diagnosis of Disseminated Lyme Borreliosis.
A study testing Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme disease in people with Lyme Disease, run by University Hospital, Strasbourg, France at 1 site in France.
Trial summary
Lyme borreliosis is a bacterial multisystemic infection transmitted by an Ixodes tick. It affects the skin, the joint and the brain. At the early phase, the diagnosis is clinical, relying on the presence of an erythema migrans at the site of the tick bite. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lyme Disease
- What is being tested?
- Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme disease
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- 7 Jul 2021to 7 Jul 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject over 18 years of age
- Subject informed of the results of the previous medical examination and informed about research objectives and risks
- Subject affiliated to a social health insurance
- Subject having signed informed consent
- Subject with clinical and serological criteria that meet the criteria of French societies, published in May and June 2019 (Jaulhac et al., 2019) as well as the European criteria of ESGBOR, corresponding to a disseminated infection of Lyme borreliosis.
- Clinical Criteria:
Show all 12Show fewer
- acute or subacute meningoradiculitis in a subject exposed to tick bites
- Uni- or bilateral peripheral facial paralysis in a subject exposed to tick bites
- Chronic radiculitis table compatible with Lyme borreliosis
- mono- or oligo arthritis of large jointsin the absence of other obvious diagnosis (inflammatory rheumatism flares, microcrystalline arthritis…)
- Skin changes suggestive of acrodermatitis chronica atrophicans
- Serological criteria: positivity for Lyme serology (two-tiered, IgG)
Who cannot join
- contraindication to performing a skin biopsy
- contraindication to local lidocaine anaesthesia with or without adrenaline
- contraindication to dermocorticoids (hypersensitivity)
- antibiotic treatment for borreliosis already administered
- inability to provide informed information
- Subject under safeguard of justice
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Les Hôpitaux Universitaires de Strasbourg
Strasbourg, 67091
Benoît JAULHAC, +33 3 69 55 14 49, benoit.jaulhac@chru-strasbourg.fr
Nathalie BOULANGER, +33 3 69 55 14 49, nathalie.boulanger@chru-strasbourg.fr
About this study
Official title: Diagnosis of Disseminated Lyme Borreliosis by Targeted Proteomics
Lyme borreliosis is a bacterial multisystemic infection transmitted by an Ixodes tick. It affects the skin, the joint and the brain. At the early phase, the diagnosis is clinical, relying on the presence of an erythema migrans at the site of the tick bite. The diagnosis of disseminated infections, more difficult to assess, mainly relies on indirect diagnosis test, i.e. serology.
This study will evaluate a new direct diagnosis method based on proteomics, which aims to demonstrate proteins of live bacteria in the skin and the synovial or cerebrospinal fluids in a direct manner.
Read the detailed description
Lyme borreliosis is a multisystemic bacterial infection affecting the skin, the joint and the nervous system. It has been shown that the skin is an essential interface as a site of bacteria inoculation and multiplication. In mouse acutely infected with different Borrelia species, the investigators have detected several protein markers of active infection in the skin by discovery proteomics, which allowed us to design a subsequent targeted proteomics assay. The invcestigators tested the same techniques in skin biopsies of humans presenting with an erythema migrans. Most of the bacterial proteins previously identified in the skin of infected mice were also detected in biopsies of human lesional skin.
The diagnosis of disseminated Lyme borreliosis currently mainly relies on evocative clinical symptoms along with a positive Borrelia serology. However, a positive serological test does not prove an active infection but merely reflects exposure to the pathogen, which is quite common in endemic regions and thus lacks positive predictive value. Moreover, direct bacteriological diagnosis tools such as culture and nucleic acid amplification (PCR) currently lack sensitivity. Planning to test the ability of proteomics to assist in the diagnosis of disseminated Lyme borreliosis, we have first developed a model of late infection in mouse, and achieved the identification of several bacterial proteins as markers of ongoing infection in the murine skin.
The investigators now wish to investigate whether the skin also constitutes a reservoir for these bacteria during persistent disseminated infection in humans, and if they can detect bacterial proteins in this easily accessible tissue by the same approach. They will directly look for bacterial proteins by selected reaction monitoring-mass spectrometry (SRM-MS), the method successfully employed in early infection setting. The ability to detect borrelial proteins in synovial fluid (patients with Lyme arthritis), cerebrospinal fluid (patients with Lyme neuroborreliosis) or lesional skin (patients with acrodermatitis chronica atrophicans) will also be investigated, as appropriated.
To improve the detection of Borrelia proteins in healthy-looking skin, a dermocorticoid will be prealably applied for a short 2-days course, a procedure the investigators demonstrated both useful and safe in mice. Since tick bite mainly occurs in the lower part of the body, the upper part of the thigh will be the site of topical steroids application and skin biopsy .
The proteomics yield will be compared to the two main other methods of direct detection, i.e. culture and PCR.
- Conditions
- Lyme Disease
- Being tested
- Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme disease
- Keywords
- targeted proteomics, skin biopsy, biomarker
- Medical subject headings
- Lyme Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme diseaseProcedure or surgery
Following a 2-days course of local daily clobetasol propionate 0,05% cream application, a skin biopsy (3 mm punch-biopsy ) of healthy-looking skin of the upper part of the thigh will be performed in all patients,.
Arthrocentesis (in patients with Lyme arthritis only) and lumbar puncture to collect cerebrospinal fluid (in patients with neuroborreliosis only) will be performed in the usual care setting as appropriated.
All biological samples will be subject to Borrelia culture, PCR and SRM-MS proteomics.
| Study group | Role | What they receive |
|---|---|---|
| Disseminated Lyme infection | Experimental | Only patients presenting with disseminated Lyme borreliosis will be part of the study. Receives: Procedure: Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Direct diagnosis of disseminated Lyme disease by proteomics
- Detection or not of targeted proteins by SRM-MS in healthy-looking skin samples of patients with disseminated Lyme borreliosis (either clinical presentation)
- Detection or not of targeted borrelial proteins by SRM-MS in synovial fluid of patients with Lyme arthritis
- Detection or not of targeted borrelial proteins by SRM-MS incerebrospinal fluid of patients with neuroborreliosis
- Detection or not of targeted borrelial proteins by SRM-MS in lesional skin of patients with acrodermatitis chronica atrophicans
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start7 Jul 2021
- Primary completion7 Jul 2021
- Study completion7 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lyme DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, Strasbourg, FranceThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benoît JAULHAC, Principal investigator, Hôpitaux Universitaires de Strasbourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04719962
- Sponsor's protocol ID
- 7609
- Acronym
- DIALYD
- Status last verified
- May 2022
- First submitted
- 18 Jan 2021
- Last updated
- 11 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnosis of Disseminated Lyme Borreliosis by Targeted Proteomics
- ClinicalTrials.gov ID
- NCT04719962
- Acronym / sponsor ID
- DIALYD / 7609
- Conditions
- Lyme Disease
- Keywords
- targeted proteomics, skin biopsy, biomarker
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 7 Jul 2021 (actual)
- Primary completion
- 7 Jul 2021 (actual)
- Study completion
- 7 Jul 2022 (estimated)
- First posted
- 22 Jan 2021 (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.
Lyme borreliosis is a bacterial multisystemic infection transmitted by an Ixodes tick. It affects the skin, the joint and the brain. At the early phase, the diagnosis is clinical, relying on the presence of an erythema migrans at the site of the tick bite. The diagnosis of disseminated infections, more difficult to assess, mainly relies on indirect diagnosis test, i.e. serology.
This study will evaluate a new direct diagnosis method based on proteomics, which aims to demonstrate proteins of live bacteria in the skin and the synovial or cerebrospinal fluids in a direct manner.
Detailed description
Lyme borreliosis is a multisystemic bacterial infection affecting the skin, the joint and the nervous system. It has been shown that the skin is an essential interface as a site of bacteria inoculation and multiplication. In mouse acutely infected with different Borrelia species, the investigators have detected several protein markers of active infection in the skin by discovery proteomics, which allowed us to design a subsequent targeted proteomics assay. The invcestigators tested the same techniques in skin biopsies of humans presenting with an erythema migrans. Most of the bacterial proteins previously identified in the skin of infected mice were also detected in biopsies of human lesional skin.
The diagnosis of disseminated Lyme borreliosis currently mainly relies on evocative clinical symptoms along with a positive Borrelia serology. However, a positive serological test does not prove an active infection but merely reflects exposure to the pathogen, which is quite common in endemic regions and thus lacks positive predictive value. Moreover, direct bacteriological diagnosis tools such as culture and nucleic acid amplification (PCR) currently lack sensitivity. Planning to test the ability of proteomics to assist in the diagnosis of disseminated Lyme borreliosis, we have first developed a model of late infection in mouse, and achieved the identification of several bacterial proteins as markers of ongoing infection in the murine skin.
The investigators now wish to investigate whether the skin also constitutes a reservoir for these bacteria during persistent disseminated infection in humans, and if they can detect bacterial proteins in this easily accessible tissue by the same approach. They will directly look for bacterial proteins by selected reaction monitoring-mass spectrometry (SRM-MS), the method successfully employed in early infection setting. The ability to detect borrelial proteins in synovial fluid (patients with Lyme arthritis), cerebrospinal fluid (patients with Lyme neuroborreliosis) or lesional skin (patients with acrodermatitis chronica atrophicans) will also be investigated, as appropriated.
To improve the detection of Borrelia proteins in healthy-looking skin, a dermocorticoid will be prealably applied for a short 2-days course, a procedure the investigators demonstrated both useful and safe in mice. Since tick bite mainly occurs in the lower part of the body, the upper part of the thigh will be the site of topical steroids application and skin biopsy .
The proteomics yield will be compared to the two main other methods of direct detection, i.e. culture and PCR.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Disseminated Lyme infection | Experimental | Procedure: Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme diseaseOnly patients presenting with disseminated Lyme borreliosis will be part of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subject over 18 years of age
- Subject informed of the results of the previous medical examination and informed about research objectives and risks
- Subject affiliated to a social health insurance
- Subject having signed informed consent
- Subject with clinical and serological criteria that meet the criteria of French societies, published in May and June 2019 (Jaulhac et al., 2019) as well as the European criteria of ESGBOR, corresponding to a disseminated infection of Lyme borreliosis.
Key exclusion criteria (6 listed)
- contraindication to performing a skin biopsy
- contraindication to local lidocaine anaesthesia with or without adrenaline
- contraindication to dermocorticoids (hypersensitivity)
- antibiotic treatment for borreliosis already administered
- inability to provide informed information
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 |
|---|---|---|
| Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme diseaseFollowing a 2-days course of local daily clobetasol propionate 0,05% cream application, a skin biopsy (3 mm punch-biopsy ) of healthy-looking skin of the upper part of the thigh will be performed in all patients,. Arthrocentesis (in patients with Lyme arthritis only) and lumbar puncture to collect cerebrospinal fluid (in patients with neuroborreliosis only) will be performed in the usual care setting as appropriated. All biological samples will be subject to Borrelia culture, PCR and SRM-MS proteomics. | Procedure or surgery | Disseminated Lyme infection |
Primary outcome
Direct diagnosis of disseminated Lyme disease by proteomics
Time frame: 6 months
1. Detection or not of targeted proteins by SRM-MS in healthy-looking skin samples of patients with disseminated Lyme borreliosis (either clinical presentation) 2. Detection or not of targeted borrelial proteins by SRM-MS in synovial fluid of patients with Lyme arthritis 3. Detection or not of targeted borrelial proteins by SRM-MS incerebrospinal fluid of patients with neuroborreliosis 4. Detection or not of targeted borrelial proteins by SRM-MS in lesional skin of patients with acrodermatitis chronica atrophicans
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Individual participant dataSharing planned: Undecided
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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.
Benoît JAULHAC principal investigator
Hôpitaux Universitaires de Strasbourg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted proteomics in skin +/- cerebrospinal or synovial fluid to diagnose disseminated Lyme disease in people with Lyme Disease, run by University Hospital, Strasbourg, France at 1 site in France.
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 12 inclusion and 6 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 May 2022. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benoît JAULHAC (+33 3 69 55 14 52, Benoit.jaulhac@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Direct diagnosis of disseminated Lyme disease by proteomics (time frame: 6 months). 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 May 2022.