Cognitive Training + D-cycloserine for Tinnitus

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Sedatives, Hypnotics, Narcotics, Opiates

Disqualifiers: Neurological conditions, Psychiatric disorders, Others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new approach, combining a medication and a brain-training computer program (Cognitive Training), can help people with chronic bothersome tinnitus (persistent ringing in the ears). The medication, d-cycloserine, originally an antibiotic, might enhance memory and learning, potentially aiding tinnitus relief when paired with mental exercises on the computer. Half of the participants will take d-cycloserine, while the other half will receive a placebo. This trial suits individuals who have experienced non-pulsatile tinnitus for at least six months, find it bothersome, and can commit to using a computer program for an hour twice a week. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you do not take any medications that are contraindicated (not recommended) with d-cycloserine or any medications that may affect cognition, such as sedatives, hypnotics, narcotics, and opiates. If you are on such medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that d-cycloserine, originally developed as an antibiotic, might aid learning and memory. This discovery has prompted scientists to explore its potential use for other conditions, such as tinnitus (a ringing or buzzing in the ears).

Regarding safety, various studies have tested d-cycloserine. Some studies found it can cause side effects like headaches, dizziness, and confusion. More serious effects, such as seizures and hallucinations, are rare but possible. These reactions are uncommon and often depend on the dose and individual response.

Since this trial is in its second phase, some evidence suggests that d-cycloserine is fairly safe for humans, but further research is needed for confirmation. Prospective participants should consider these points and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for chronic bothersome tinnitus, which often involve sound therapy or medication to manage symptoms, this new approach combines cognitive training with D-cycloserine, a drug that may enhance learning and memory. Researchers are excited because D-cycloserine, traditionally used in antibiotic treatments, is being repurposed here to potentially boost the effectiveness of cognitive training by facilitating neural plasticity. This combination could provide a more targeted way to reduce tinnitus symptoms by directly engaging the brain's learning processes, offering hope for faster and more sustainable relief.

What evidence suggests that this trial's treatments could be effective for tinnitus?

Research has shown that d-cycloserine can improve memory and learning. In studies involving individuals with schizophrenia, d-cycloserine enhanced memory. In this trial, some participants will receive d-cycloserine to determine if it can enhance the effectiveness of mental exercises for tinnitus (ringing in the ears). These exercises aim to improve memory and attention, potentially reducing tinnitus symptoms. The overall goal is to assess whether combining d-cycloserine with these exercises leads to better outcomes for people with tinnitus. ^{6 7 8 9 10}

Who Is on the Research Team?

Jay F Piccirillo, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Participants must be between the ages of 35 and 65.

Participants must have subjective, unilateral or bilateral, non-pulsatile tinnitus for at least a duration of 6 consecutive months.

Participants must have bothersome tinnitus as defined by a THI ≥ 30.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cognitive training with either d-cycloserine or placebo for 5 weeks

5 weeks

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Training
• D-cycloserine

How Is the Trial Designed?

Group I: d-cycloserine Active Control 1 Intervention

d-cycloserine 250 mg two days per week one hour prior to(cognitive training)

Group II: Placebo Placebo Group 1 Intervention

Placebo pill two days per week 1 hour prior to cognitive training

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study involving 46 young adults with mild depressive symptoms, executive functioning and processing speed (EF/PS)-focused computerized cognitive training (CCT) led to greater improvements in those specific cognitive areas compared to verbal ability-focused CCT.

Both types of CCT resulted in significant improvements in mood and everyday functioning, but the EF/PS group achieved similar mood benefits with only half the training time, suggesting that the content of CCT may not be as crucial as the engagement in the training itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in young adults with depressive symptoms: Effects on mood, cognition, and everyday functioning. Motter, JN., Grinberg, A., Lieberman, DH., et al.[2019]

A study involving 60 patients with mild cognitive impairment and mild Alzheimer's disease found that adding a computer-based cognitive training (CBCT) program to traditional cognitive training (TCT) significantly reduced anxiety symptoms and improved decision-making after 12 months.

While the CBCT + TCT group showed benefits in anxiety and decision-making, there were no significant changes in basic cognitive functions, suggesting that patients already receiving TCT may have reached a performance ceiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of an adjunctive computer-based cognitive training program in amnestic mild cognitive impairment and Alzheimer's disease: a single-blind, randomized clinical trial. Gaitán, A., Garolera, M., Cerulla, N., et al.[2022]

Home-based Computerized Cognitive Training (CCT) tailored to individual needs significantly improved cognitive functions such as memory and learning in older adults with mild cognitive impairment (MCI) and mood-related neuropsychiatric symptoms (MrNPS) over an 8-12 week period.

Participants in the CCT group not only showed enhanced cognitive performance but also reported improved mood and reduced caregiver burden compared to those in the active control group, indicating broader benefits beyond just cognitive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored and Adaptive Computerized Cognitive Training in Older Adults at Risk for Dementia: A Randomized Controlled Trial. Bahar-Fuchs, A., Webb, S., Bartsch, L., et al.[2022]

This study aims to systematically review and analyze the efficacy of computerized cognitive training (CCT) in improving cognitive performance in adults with depression, focusing on randomized controlled trials.

The research will explore how CCT affects not only cognitive outcomes but also mood and daily functioning, making it the first comprehensive analysis of its kind in this specific clinical population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computerized cognitive training in people with depression: a protocol for a systematic review and meta-analysis. Lampit, A., Launder, NH., Minkov, R., et al.[2022]

The RehaCom computerized cognitive training program significantly improved attention and memory functions in 50 brain injury patients after 60 training sessions, with all patients showing enhanced performance in the targeted areas.

The program was well-tolerated, with no reported negative effects such as mental fatigue, headache, or eye irritation, indicating its safety for use in rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of RehaCom software for cognitive rehabilitation of patients with acquired brain injury. Fernández, E., Bringas, ML., Salazar, S., et al.[2022]

Computer-assisted cognitive training has been shown to be an effective tool in neurological rehabilitation, particularly for patients with attention deficits, as it allows for precise stimulus representation and reaction time measures.

This type of training is most beneficial when integrated into a comprehensive therapeutic framework, enhancing the overall rehabilitation process and ensuring sufficient therapeutic intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Computer-assisted neuropsychological training in neurological rehabilitation]. Reuter, BM., Schönle, PW.[2006]

Computerized cognitive training (CCT) using Brain HQ showed significant cognitive improvements in psychiatric rehabilitation clients, with an average increase of 4.4 points in BACS t-scores after about 17 days of training.

Higher engagement in training (measured by levels completed per day) was positively correlated with cognitive gains, suggesting that monitoring engagement can help identify patients who may need additional support to benefit from CCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training engagement, baseline cognitive functioning, and cognitive gains with computerized cognitive training: A cross-diagnostic study. Harvey, PD., Balzer, AM., Kotwicki, RJ.[2020]

Thirty patients with chronic cognitive deficits post-stroke participated in a study comparing two types of Computerized Cognitive Training (CCT) over 6 weeks, showing that both types led to improvements in cognitive functioning.

Group A, which received customized CCT, reported fewer subjective complaints, while Group B, which received non-customized CCT, showed better performance-based improvements, indicating that both tailored and standard CCT can be beneficial for cognitive recovery in chronic stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional improvement in chronic stroke patients when following a supervised home-based computerized cognitive training. Gil-Pagés, M., Solana, J., Sánchez-Carrión, R., et al.[2023]

The trial involved 18 adolescents with ADHD over a 7-week period, comparing computerized cognitive exercises from Scientific Brain Training (SBT) to the game Tetris as an active placebo.

While no significant differences were found between the two groups, SBT showed a significant improvement in sustained attention, and Tetris improved working memory, indicating that both interventions may have beneficial effects on cognitive functions in adolescents with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized pilot trial comparing computerized cognitive exercises to Tetris in adolescents with attention-deficit/hyperactivity disorder. Bikic, A., Christensen, TØ., Leckman, JF., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5514293/

A Novel Treatment for Tinnitus and ... Our overall research hypothesis was that a neuroplasticity-sensitizing medication (D-cycloserine), compared with placebo, would lead to greater improvements in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01550796

Treatment of Chronic Bothersome Tinnitus Using Cognitive ... The purpose of this research study is to determine if a medication along with a computer program designed to improve memory and other mental processes can ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4547356/

D-Cycloserine Augmentation of Cognitive Remediation in ... D-cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S092099641400019X

d-Cycloserine augmentation of cognitive remediation in ... d-Cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002%2Fda.23242

Efficacy of D‐cycloserine augmented brief intensive ... DCS augmented intensive exposure therapy did not result in overall additional benefits relative to placebo. Intensive exposure proved effective ...

6. fishersci.com fishersci.com/store/msds?partNumber=AC228480010&countryCode=US&language=en

SAFETY DATA SHEET Physical State. Powder Solid. Appearance. Off-white. Odor. Odorless. Odor Threshold. No information available. pH. 5.5-6.5 10% aq. sol.

7. carlroth.com carlroth.com/medias/SDB-CN37-MT-EN.pdf?context=bWFzdGVyfHNlY3VyaXR5RGF0YXNoZWV0c3wyMzQ3MTl8YXBwbGljYXRpb24vcGRmfGFEZzRMMmcxTmk4NU1UYzNORFU1TnpVeU9Ua3dMMU5FUWw5RFRqTTNYMDFVWDBWT0xuQmtaZ3xjMGIwMjM2NzI3MTM1OWViZTBjNjg0NzMwNjhmYTE3ZGU0ZjUxOGM5MmU3YmMzZWQ0MmQxODQxNmQ5YjcxOTI2

Safety Data Sheet: D-Cycloserine Uses advised against: Do not use for private purposes (household). Food, drink and animal feedingstuffs. 1.3. Details of the supplier of the safety data sheet.

8. sigmaaldrich.com sigmaaldrich.com/US/en/sds/SIGMA/C6880?srsltid=AfmBOop3pdGnv15kExiNZEDSTg8Qv9KQEknnQM-zBkTA0zIwnLavd_YB

SAFETY DATA SHEET Chemical stability. : The product is chemically stable under standard ambient conditions (room temperature) . Possibility of hazardous reactions.

9. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/22194m.pdf

Safety Data Sheet If this product is combined with other materials, deteriorates, or becomes contaminated, it may pose hazards not mentioned in this SDS.

10. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ad9d0d-3f3e-4116-8bc4-8d76da4b75ae

Label: SEROMYCIN- cycloserine capsule - DailyMed Toxic effects may include headache, vertigo, confusion, drowsiness, hyperirritability, paresthesias, dysarthria, psychosis paresis, convulsions, and coma.