Clinical trial NCT06915324: Transcranial Direct Current Stimulation for Post Treatment Lyme Disease
Official title: Transcranial Direct Current Stimulation (tDCS) of Brain Fog in Patients With Post Treatment Lyme Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-Treatment Lyme Disease
Keywords: tDCS
Cognitive training
Neuromodulation
Brain Fog
Brain Stimulation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Steven & Alexandra Cohen Foundation
First posted: 2025-04-08
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants receive computer-based cognitive exercises to improve processing speed. During the cognitive exercises, half of the participants receive concomitant active tDCS while the other half of the participants receive concomitant sham tDCS.
Primary purpose: TREATMENT

Brief summary: The primary purpose of this pilot study is to investigate a novel approach to the treatment of cognitive symptoms that persist despite prior antibiotic treatment for Lyme disease (Post treatment Lyme Disease or PTLD).

Aim 1: The primary aim of this study is to assess whether the processing speed of individuals with PTLD can be enhanced by combining transcranial direct current stimulation (tDCS) with computer based cognitive training games. To achieve this aim, over a 4-week period, all individuals with PTLD will participate in at home adaptive cognitive training combined with either active stimulation or sham stimulation.

Aim 2: To determine if treatment benefit in processing speed is sustained, the study will compare the sham and active groups 8 weeks after completion of study treatment.

Detailed description: The primary purpose of this pilot study is to investigate a novel approach to the treatment of cognitive symptoms that persist despite prior antibiotic treatment for Lyme disease (Post treatment Lyme Disease or PTLD).

Processing speed has been shown to be one of the primary areas of cognition affected by PTLD and may be a critical component of "brain fog," an everyday term for the fuzzy/scattered thinking, lack of mental sharpness and forgetfulness commonly reported by PTLD patients. Deficits in processing speed may also relate to fatigue and have broader effects on other aspects of cognitive performance including problems with memory and language.

This study will enroll participants with PTLD (definitive, probable, possible) who will be randomly assigned to one of two treatment groups at a 1:1 ratio. The at-home treatment duration is 30 minutes daily for 20 sessions spanning approximately 4 weeks. Group 1 will receive active transcranial direct current stimulation (tDCS) combined with computer-based cognitive training. Group 2 will receive sham tDCS combined with computer-based cognitive training. The cognitive training exercises are personalized to each user's performance level and are aimed at improving cognitive performance by improving information processing speed.

The study will assess changes in cognitive functioning in the context of tDCS treatment using both formal neuropsychological tests as well as questionnaires regarding cognitive lapses in everyday situations. In addition, the study will be examining whether tDCS will lead to improvements in other aspects of functioning such as mood, fatigue and pain symptoms as measured by clinical rating scales.

Eligibility criteria: Inclusion Criteria:

* History of diagnosis of Lyme disease by a health care provider, meeting criteria for either definite or probable or possible LD
* Willingness to provide documentation of prior LD testing and/or related medical records
* Total prior antibiotic treatment for LD was at least 2 courses of antibiotic therapy
* Have cognitive symptoms attributed to Lyme disease that have persisted or returned despite antibiotic therapy
* Current cognitive symptoms interfere with function and/or cause distress
* Have evidence of slowed processing speed on a screening measure
* Participant is willing to be off of antibiotic treatment for tick-borne disease for at least 4 weeks prior to final determination of study eligibility and for the duration of the 12-week study.
* Participant expresses willingness to not start new medications that might affect treatment outcome during the trial (unless medically necessary), and willingness to inform study staff regarding any changes in medication
* Live in the US or Canada and comfortable speaking English
* Age 18-65
* Stable and continuous access to internet service
* Adequate home facilities (enough space, access to quiet and distraction free area)
* Able to commit to the 12-week study period (4 weeks of training sessions and an 8-week post treatment visit)
* Estimated intellectual ability \>= 85

Exclusion Criteria:

- Medical Illness: Any of the following: a. Unstable non-Lyme-related chronic medical illness over the last 12 months (e.g., cancer, acute myocardial infarction, labile hypertension) b. Any severe skin disorder or skin sensitive area near stimulation locations (e.g. forehead)

Neurologic: Any of the following:

* History of traumatic brain injury with persistent post-concussive symptoms
* History of seizure disorder or recent (\<5 years) seizure history
* History of neurosurgery to the head
* Chronic headaches or migraines of moderate to severe intensity within the last month
* Post stroke deficits that may interfere with assessment
* Any progressive neurodegenerative disorder or other neurological disorders that may interfere with assessment at discretion of the investigator.

Psychiatric: Any of the following:

* History of intellectual disability, or other developmental neurological condition associated with cognitive impairment
* Current primary psychiatric disorder that would interfere with ability to participate
* Current alcohol or other substance use disorder
* Current suicide risk as assessed by the C-SSRS (any level)
* History of suicidal behavior over the last year
* History of a diagnosis of a psychotic disorder, mania or bipolar disorder
* Depression rating of moderate or severe at screening

  * Currently taking opiate-based medications, dissociative drugs (prescribed or illicit), or other medication considered likely to interfere with treatment outcome at the discretion of the investigator. The use of a stable dose of benzodiazepines, anticholinergic agents and non-narcotic pain medications is permitted. The use of an occasional dose of these medications is also permitted, but not within 48 hours of neurocognitive study assessments.
  * Participants whose current daily medication regimen has not been stable for a minimum of 4 weeks prior to final determination of study eligibility
  * Medical device implanted in the head (such as a Deep Brain Stimulator) or in the neck (such as a Vagus Nerve Stimulator), or metal implants in the head or neck
  * Inadequate visual or motor skills needed for regular computer use or to operate study equipment, or inability to provide informed consent
  * Individuals who are pregnant or breastfeeding or planning to become pregnant
  * Lifestyle Considerations: Participants not willing to refrain from beginning, resuming or increasing non study cognitive training or cognitive enhancing supplements/medications or other therapies that might affect treatment outcome

Primary outcomes:
measure: Coding test scale score for acute treatment
timeFrame: 4 weeks
measure: Coding test scale score for post-treatment follow-up
timeFrame: 12 weeks
Secondary outcomes:
measure: Composite score of the reaction time measures
timeFrame: 4 weeks
measure: Fatigue Severity Scale (FSS) Score
timeFrame: 4 weeks
measure: General Symptom Questionnaire (GSQ-30) Score
timeFrame: 4 weeks
measure: Generalized Anxiety Disorder-7 (GAD-7) Score
timeFrame: 4 weeks
measure: PROMIS Emotional Distress-Depression-Short Form Score
timeFrame: 4 weeks
measure: Patient-Reported Outcomes Measurement Information System (PROMIS-29) symptom summary score
timeFrame: 4 weeks
measure: Cognitive functioning z-score
timeFrame: 4 weeks
measure: Neuro-QoL Short Form v1.0 - Applied Cognition Score
timeFrame: 4 weeks
measure: Brain Fog Visual Analogue Scale (Brain Fog VAS) Score
timeFrame: 4 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Department of Psychiatry
state: New York
Study officials:
affiliation: Columbia University
name: Brian A Fallon, MD
role: PRINCIPAL_INVESTIGATOR
References: