Gene Expression Profiles in Spinal Tuberculosis.

NCT05610098 | Recruiting

• 2 other identifiers: HREC 243/2022AOS-DIA-22-029-TRA
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tuberculosis, Spinal; Tuberculosis, Osteoarticular; Tuberculosis; Mycobacterium Infections; Infections; Bone Diseases, Infectious; Musculoskeletal Diseases; Spinal Disease; Spondylitis; Spondylitis; Tuberculosis (Manifestation); Spondylodiscitis; Positron-Emission Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures

Keywords

Spinal TB; tuberculous spondylodiscitis; FDG-PET/CT; POC

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  3 years

Secondary Outcomes (3)

• MRI vs. PET/CT at the site of disease (spine level)

  3 years

• Whole Genome Sequencing of Mtb. isolates

  3 years

• PET/CT changes over 12 months

  3 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cape Town: lead
• University of Zurich: collaborator

Study Sites (1)

Groote Schuur Hospital

Cape Town, Western Cape, 7935, South Africa

RECRUITING

Related Publications (1)

• 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.

  PMID: 38918806 DERIVED

Related Links

• General Medicine \& Global Health research group at the University of Cape Town

Biospecimen

Retention: SAMPLES WITH DNA

Site of disease specimen collection (sputum, spinal abscess/disc/bone tissue collection); whole-blood samples, serum, PBMC, Paxgene.

MeSH Terms

Conditions

Tuberculosis, Spinal; Tuberculosis, Osteoarticular; Tuberculosis; Mycobacterium Infections; Infections; Bone Diseases, Infectious; Musculoskeletal Diseases; Spinal Diseases; Spondylitis; Discitis

Condition Hierarchy (Ancestors)

Tuberculosis, Extrapulmonary; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Bone Diseases

Study Officials

• friedrich Thienemann, MD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Friedrich F Thienemann, MD

CONTACT

+27 (0)21 406 6358; friedrich.thienemann@uct.ac.za

Michael Held, MD

CONTACT

+27 (0)21 406 6358; michael.held@uct.ac.za

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal Investigator and Research Group Leader

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: November 9, 2022
• Study Start: October 25, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 23, 2024

Record last verified: 2024-08

Locations

ZA (1)