Tuberculosis, SpinalSpinalTBXNCT05610098
Gene Expression Profiles in Spinal Tuberculosis.
An observational study of Tuberculosis, Spinal and Tuberculosis, Osteoarticular, run by University of Cape Town at 1 site in South Africa.
Trial summary
Tuberculosis (TB) is one of the top ten causes of death worldwide with approximately 10 million cases globally and 1.2 million deaths. Sub-Saharan Africa carries the highest burden of TB. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Spinal, Tuberculosis, Osteoarticular, Tuberculosis
- How many people
- 100 participants
- Where
- 1 siteSouth Africa
- Study dates
- 25 Oct 2022to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Participants with clinically and MR-suspected spinal TB will be recruited from the Department of Orthopaedics, Groote Schuur Hospital, Cape Town, South Africa. According to the current caseload, the investigators will be able to include 50-100 participants per year, aiming for 100 participants in total. In result, the investigators are aiming for 300 PET/CTs (100 initial, 100 at 6 months, 100 at 12 months) and 300 peripheral blood samples for gene expression analysis.
Who may be able to join
- Participant has completed the written informed consent process prior to undergoing any clinical evaluations and willing to undergo HIV testing
- TB spine based on clinical and radiological criteria
- Age 18 or older with a body weight of at least 40 kg body weight
- Able and willing to return to follow-up
- Willing to have samples, including DNA including RNA extraction, stored
- Willing to consistently practice a highly reliable method of pregnancy prevention
Who cannot join
- Pregnancy or active desire to become pregnant within the next 6 months.
- Uncontrolled diabetes (HbA1c ≥ 6.5% / random glucose concentration ≥11.1 mmol/l, fasting plasma glucose ≥ 7.0 mmol/l)
- Alcohol and substance abuse which might interfere with medication adherence during the trial
- Positive SARS-CoV-2 PCR in the past 4 weeks
- Suspicion of malignancy on MRI or known malignancy
- Suspicion of inflammatory disease and other rheumatological conditions
- Any person for whom the physician feels this study is not appropriate
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa1 site, 1 recruiting
- Recruiting
Groote Schuur Hospital
Cape Town, Western Cape, 7935
Julian F Scherer, MD, +27762030775, schjul017@myuct.ac.za
Friedrich Thienemann, Prof
About this study
Official title: Comparing Gene Expression Profiles of Adults With Isolated Spinal TB to Disseminated Spinal TB Identified by 18FDG-PET/CT at Time of Diagnosis, 6-and 12-months Follow-up
Tuberculosis (TB) is one of the top ten causes of death worldwide with approximately 10 million cases globally and 1.2 million deaths. Sub-Saharan Africa carries the highest burden of TB. South Africa has one of the highest HIV and TB rates worldwide with an HIV prevalence rate in adults of 19% and a TB case notification rate of 615/100,000 in 2019. Over many years, focus has been paid to pulmonary TB and extrapulmonary TB (EPTB) has received only little attention even though it accounts for almost a quatre of all TB cases. The diagnosis of EPTB remains challenging simply because sample collection requires invasive procedures in the absence of a blood-based diagnostic test. Spinal TB (spondylitis or spondylodiscitis caused by Mycobacterium tuberculosis) - often known as Pott's disease - accounts for up to 10% of EPTB and affects young children, people with HIV-coinfection and elderly, and often leads to lifelong debilitating disease due to devastating deformation of the spine and compression of neural structures. Little is known with regards to the extent of disease and isolated TB spine as well as a disseminated form of TB spine have been described. The latter presents with a spinal manifestation plus disseminations to other organs such as the lungs, pleura, lymph nodes, the GIT or urinary tract or even the brain.
In the Spinal TB X cohort, the investigators aim to describe the clinical phenotype of spinal TB using whole body PET/CT and identify a specific gene expression profile for the different stages of dissemination and compare findings to previously described signatures for latent and active pulmonary TB. A blood-based test for spinal TB would lead to earlier diagnosis and treatment in all settings globally and improve treatment outcome of this devastating disease.
Read the detailed description
In the Spinal TB X cohort, the investigators aim to describe the clinical phenotype of spinal TB using whole body PET/CT and identify a specific gene expression profile for the different stages of dissemination and compare findings to previously described signatures for latent and active pulmonary TB. A blood-based test for spinal TB would lead to earlier diagnosis and treatment in all settings globally and improve treatment outcome of this devastating disease.
- The investigators hypothesize that spinal TB may present as two clinical phenotypes: isolated spinal TB with no additional lesion on whole body PET/CT and disseminated spinal TB with a spinal lesion plus an additional extraspinal lesion on whole body PET/CT.
- The investigators hypothesize that a specific gene expression profile may distinguish between the two clinical entities above and allows for treatment monitoring during antimicrobial therapy ("personalized medicine")
- The investigators hypothesize that whole body PET/CT is superior to MRI in diagnosing spinal and extraspinal TB.
Primary objective
To describe the clinical phenotype of spinal TB using whole body PET/CT and to identify mRNA gene expression profiles of isolated spinal TB versus disseminated spinal TB stratified by HIV status.
Secondary objectives
- To identify the distributive patterns of suspected spinal TB using two imaging modalities: MRI and PET/CT.
- To analyse the genomes of Mtb. extracted from different sites of the body (if available) and to identify differences in their genome regarding SNPs and drug sensibility.
- To analyse imaging findings using PET/CT at treatment initiation, 6 months, and 12 months to better understand treatment outcome using PET/CT.
- To compare imaging findings on PET/CT and MRI at baseline to evaluate the role of PET/CT in spinal TB diagnostics (virtual biopsy).
Design
This is a prospective cohort study to develop new diagnostics for isolated spinal TB versus disseminated spinal TB and treatment monitoring. Furthermore, this study investigates genetic variability in spinal TB and its distributional pattern. After MRI-confirmation of spinal TB according to local algorithms, patients will be included in the study. At baseline, clinical examination as well as blood collection will be performed. Every patient with no confirmed HIV will undergo HIV-testing. Sputum will be collected and screening for diabetes and pregnancy will be completed. Whole-body PET/CTs will be performed at 0 months, 6 months, and 12 months. Spinal biopsies will be gathered if surgery is being performed. Samples of the sites of disease will be acquired if applicable and TB culture as well as GeneXpert will be performed.
Recruitment
Patients with newly diagnosed spinal TB at the Department of Orthopaedics, Groote Schuur Hospital, Cape Town, South Africa.
- Conditions
- Tuberculosis, Spinal, Tuberculosis, Osteoarticular, Tuberculosis, Mycobacterium Infections, Infections, Bone Diseases, Infectious
- Keywords
- Spinal TB, tuberculous spondylodiscitis, FDG-PET/CT, POC
- Medical subject headings
- Tuberculosis, Spinal, Tuberculosis, Osteoarticular, Tuberculosis, Mycobacterium Infections, Infections, Bone Diseases, Infectious, Musculoskeletal Diseases, Spinal Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical phenotype of spinal TB
To describe the clinical phenotype of spinal TB using whole body PET/CT a semiquantitative approach will be used. Regions of interest (ROIs) will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software
Measured: 3 years
mRNA gene expression profiles of spinal TB
mRNA gene expression profiles of isolated spinal TB versus disseminated spinal TB described in outcome 1 will be measured and stratified by HIV status.
Measured: 3 years
Secondary outcomes (3)
MRI vs. PET/CT at the site of disease (spine level)
To identify the distributive patterns of suspected spinal TB using two imaging modalities: MRI and PET/CT. MRI is measure T1, T2 and diffusion weighted images. Regions of interest (ROIs) in the spine will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software
Measured: 3 years
Whole Genome Sequencing of Mtb. isolates
To analyse the genomes of Mtb. extracted from different sites of the body (if available) and to identify differences in their genome regarding SNPs and drug sensibility.
Measured: 3 years
PET/CT changes over 12 months
Regions of interest (ROIs) in the spine will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software at different timepoints: treatment initiation, 6 months, and 12 months
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2022
- Study start25 Oct 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, SpinalStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- University of Zurich
- Responsible party
- Principal investigator, Prof Friedrich Thienemann, University of Cape Town
- Investigators
- friedrich Thienemann, MD, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05610098
- Sponsor's protocol ID
- HREC 243/2022
- Other IDs
- AOS-DIA-22-029-TRA
- Acronym
- SpinalTBX
- Status last verified
- Aug 2024
- First submitted
- 24 Oct 2022
- Last updated
- 23 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Scherer J, Mukasa SL, Wolmarans K, Guler R, Kotze T, Song T, Dunn R, Laubscher M, Pape HC, Held M, Thienemann F. Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by 18FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study). J Orthop Surg Res. 2024 Jun 25;19(1):376. doi: 10.1186/s13018-024-04840-7.
PubMed 38918806
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing Gene Expression Profiles of Adults With Isolated Spinal TB to Disseminated Spinal TB Identified by 18FDG-PET/CT at Time of Diagnosis, 6-and 12-months Follow-up
- ClinicalTrials.gov ID
- NCT05610098
- Acronym / sponsor ID
- SpinalTBX / HREC 243/2022
- Conditions
- Tuberculosis, Spinal, Tuberculosis, Osteoarticular, Tuberculosis, Mycobacterium Infections, Infections, Bone Diseases, Infectious
- Keywords
- Spinal TB, tuberculous spondylodiscitis, FDG-PET/CT, POC
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- University of Zurich
- Study start
- 25 Oct 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 9 Nov 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.
Tuberculosis (TB) is one of the top ten causes of death worldwide with approximately 10 million cases globally and 1.2 million deaths. Sub-Saharan Africa carries the highest burden of TB. South Africa has one of the highest HIV and TB rates worldwide with an HIV prevalence rate in adults of 19% and a TB case notification rate of 615/100,000 in 2019. Over many years, focus has been paid to pulmonary TB and extrapulmonary TB (EPTB) has received only little attention even though it accounts for almost a quatre of all TB cases. The diagnosis of EPTB remains challenging simply because sample collection requires invasive procedures in the absence of a blood-based diagnostic test. Spinal TB (spondylitis or spondylodiscitis caused by Mycobacterium tuberculosis) - often known as Pott's disease - accounts for up to 10% of EPTB and affects young children, people with HIV-coinfection and elderly, and often leads to lifelong debilitating disease due to devastating deformation of the spine and compression of neural structures. Little is known with regards to the extent of disease and isolated TB spine as well as a disseminated form of TB spine have been described. The latter presents with a spinal manifestation plus disseminations to other organs such as the lungs, pleura, lymph nodes, the GIT or urinary tract or even the brain.
In the Spinal TB X cohort, the investigators aim to describe the clinical phenotype of spinal TB using whole body PET/CT and identify a specific gene expression profile for the different stages of dissemination and compare findings to previously described signatures for latent and active pulmonary TB. A blood-based test for spinal TB would lead to earlier diagnosis and treatment in all settings globally and improve treatment outcome of this devastating disease.
Detailed description
In the Spinal TB X cohort, the investigators aim to describe the clinical phenotype of spinal TB using whole body PET/CT and identify a specific gene expression profile for the different stages of dissemination and compare findings to previously described signatures for latent and active pulmonary TB. A blood-based test for spinal TB would lead to earlier diagnosis and treatment in all settings globally and improve treatment outcome of this devastating disease.
- The investigators hypothesize that spinal TB may present as two clinical phenotypes: isolated spinal TB with no additional lesion on whole body PET/CT and disseminated spinal TB with a spinal lesion plus an additional extraspinal lesion on whole body PET/CT.
- The investigators hypothesize that a specific gene expression profile may distinguish between the two clinical entities above and allows for treatment monitoring during antimicrobial therapy ("personalized medicine")
- The investigators hypothesize that whole body PET/CT is superior to MRI in diagnosing spinal and extraspinal TB.
Primary objective
To describe the clinical phenotype of spinal TB using whole body PET/CT and to identify mRNA gene expression profiles of isolated spinal TB versus disseminated spinal TB stratified by HIV status.
Secondary objectives
- To identify the distributive patterns of suspected spinal TB using two imaging modalities: MRI and PET/CT.
- To analyse the genomes of Mtb. extracted from different sites of the body (if available) and to identify differences in their genome regarding SNPs and drug sensibility.
- To analyse imaging findings using PET/CT at treatment initiation, 6 months, and 12 months to better understand treatment outcome using PET/CT.
- To compare imaging findings on PET/CT and MRI at baseline to evaluate the role of PET/CT in spinal TB diagnostics (virtual biopsy).
Design
This is a prospective cohort study to develop new diagnostics for isolated spinal TB versus disseminated spinal TB and treatment monitoring. Furthermore, this study investigates genetic variability in spinal TB and its distributional pattern. After MRI-confirmation of spinal TB according to local algorithms, patients will be included in the study. At baseline, clinical examination as well as blood collection will be performed. Every patient with no confirmed HIV will undergo HIV-testing. Sputum will be collected and screening for diabetes and pregnancy will be completed. Whole-body PET/CTs will be performed at 0 months, 6 months, and 12 months. Spinal biopsies will be gathered if surgery is being performed. Samples of the sites of disease will be acquired if applicable and TB culture as well as GeneXpert will be performed.
Recruitment
Patients with newly diagnosed spinal TB at the Department of Orthopaedics, Groote Schuur Hospital, Cape Town, South Africa.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants with clinically and MR-suspected spinal TB will be recruited from the Department of Orthopaedics, Groote Schuur Hospital, Cape Town, South Africa. According to the current caseload, the investigators will be able to include 50-100 participants per year, aiming for 100 participants in total. In result, the investigators are aiming for 300 PET/CTs (100 initial, 100 at 6 months, 100 at 12 months) and 300 peripheral blood samples for gene expression analysis.
Key inclusion criteria (6 listed)
- Participant has completed the written informed consent process prior to undergoing any clinical evaluations and willing to undergo HIV testing
- TB spine based on clinical and radiological criteria
- Age 18 or older with a body weight of at least 40 kg body weight
- Able and willing to return to follow-up
- Willing to have samples, including DNA including RNA extraction, stored
Key exclusion criteria (7 listed)
- Pregnancy or active desire to become pregnant within the next 6 months.
- Uncontrolled diabetes (HbA1c ≥ 6.5% / random glucose concentration ≥11.1 mmol/l, fasting plasma glucose ≥ 7.0 mmol/l)
- Alcohol and substance abuse which might interfere with medication adherence during the trial
- Positive SARS-CoV-2 PCR in the past 4 weeks
- Suspicion of malignancy on MRI or known malignancy
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
Clinical phenotype of spinal TB
Time frame: 3 years
To describe the clinical phenotype of spinal TB using whole body PET/CT a semiquantitative approach will be used. Regions of interest (ROIs) will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software
mRNA gene expression profiles of spinal TB
Time frame: 3 years
mRNA gene expression profiles of isolated spinal TB versus disseminated spinal TB described in outcome 1 will be measured and stratified by HIV status.
3 secondary outcomes
MRI vs. PET/CT at the site of disease (spine level)
Time frame: 3 years
Whole Genome Sequencing of Mtb. isolates
Time frame: 3 years
PET/CT changes over 12 months
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
- Derived from this study: PubMed 38918806Scherer J, Mukasa SL, Wolmarans K, Guler R, Kotze T, Song T, Dunn R, Laubscher M, Pape HC, Held M, Thienemann F. Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by 18FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study). J Orthop Surg Res. 2024 Jun 25;19(1):376. doi: 10.1186/s13018-024-04840-7.
- General Medicine \& Global Health research group at the University of Cape TownLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Tuberculosis, Spinal
Not yet recruitingPhase 2
Short-Course Anti-tuberculosis Regimens for Mild Spinal Tuberculosis
Mild Spinal Tuberculosis
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.
friedrich Thienemann, MD principal investigator
University of Cape Town
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 Tuberculosis, Spinal and Tuberculosis, Osteoarticular, run by University of Cape Town at 1 site in South Africa.
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 6 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 23 Aug 2024. 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 South Africa. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Friedrich F Thienemann, MD (+27 (0)21 406 6358, friedrich.thienemann@uct.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical phenotype of spinal TB (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT05610098, which also lists 1 linked publication.
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 23 Aug 2024.