Lumbar Puncture and Syphilis Outcome

Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system in about 40% of patients with syphilis. This happens early after infection. Patients with neuroinvasion are at risk of developing serious neurological complications, including vision or hearing loss, stroke and dementia. Because neuroinvasion can happen without symptoms, the only way to identify it is by performing a lumbar puncture (LP) to examine cerebrospinal fluid (CSF).The overall hypothesis to be tested in this study is that a strategy of immediate LP, followed by therapy based on CSF evaluation, results in better serological and functional outcomes in patients with syphilis who are at high risk for neuroinvasion.

Study Overview

• Status: Completed
• Conditions: Syphilis
• Intervention / Treatment: Procedure: Lumbar puncture

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females age 18 years or older
2. Current syphilis
3. Primary language is English or English is a second language but patient self-describes as fluent in English
4. Able to provide informed consent
5. If treated with benzathine penicillin G (BPG), it must have occurred less than 14 days before the entry visit (before the first visit if there is more than one entry visit)

Exclusion Criteria:

1. Provider plans neurosyphilis (NS) treatment regardless of whether the patient has an lumbar puncture (LP)
2. Receipt of antibiotic treatment that would be effective for NS (for example, IV or intramuscular (IM) beta-lactam antibiotics [other than BPG]) within one month before study entry; single dose of IM ceftriaxone in the last month is not exclusionary
3. Allergy to penicillin or lidocaine
4. Contraindication to LP, including untreatable coagulation disorder, use of anticoagulants that cannot be temporarily discontinued, thrombocytopenia, focal neurological examination
5. Other known cause of central nervous system (CNS) infection in the last year, including that due to bacterial, fungal, protozoal or viral agents, such as tuberculosis, Cryptococcus, toxoplasmosis or herpes zoster that could confound interpretation of CSF results
6. Unlikely to be able to comply with study requirements or complete the study, for example, planning to leave the area < 6 months after enrollment
7. Subjects will not be allowed to re-enroll in this study with a new episode of syphilis

Individuals who are unwilling to be randomized can choose LP or no LP. Eligibility criteria for these individuals are:

1. 18 years of age or older
2. Current syphilis infection
3. Primary language is English or fluent in English
4. No contraindications to LP
5. Have not received antibiotics within one month that would treat neurosyphilis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: LP; Participants undergo lumbar puncture for CSF evaluation	Procedure: Lumbar puncture
No Intervention: No LP; Participants do not undergo lumbar puncture and CSF is not examined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appropriate Decline in Serum Rapid Plasma Reagin Test (RPR) Titer	Decline in serum RPR titer by four-fold or to nonreactive at 6 months (+/- 4 weeks) in early syphilis or at 12 months (+/- 4 weeks) in late syphilis. This is the definition of treatment success according to the US Centers for Disease Control and Prevention guidelines.	6-12 months +/- 4 weeks
Time to Improvement in Performance on CogState Battery.	Assessment of cognitive impairment was based on age adjusted normative data from CogState and was categorized as none (all test scores > -1 standard deviation [SD] of normative data), mild impairment (two test scores < -1 SD, or one test score < -2 SD), moderate impairment (two test scores < -2 SD) or severe impairment (three test scores < -2 SD). Participants were categorized as improved if they had any impairment at study entry and improved by at least one category.	6-12 months +/- 4 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Christina M Marra, MD, University of Washington

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 8, 2014
• First Posted (Estimate): January 9, 2014

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Syphilis
• Other Study ID Numbers: STUDY00001718; R01NS082120 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No