CLINICAL TRIALS PROFILE FOR CYCLOSERINE

All Clinical Trials for Cycloserine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000194 ↗	Neurobiology of Opioid Dependence: 3 - 3	Withdrawn	National Institute on Drug Abuse (NIDA)	Phase 2	1993-01-01	The purpose of this study is to study the effects of cycloserine on naloxone-precipitated opiate withdrawal.
NCT00000194 ↗	Neurobiology of Opioid Dependence: 3 - 3	Withdrawn	Yale University	Phase 2	1993-01-01	The purpose of this study is to study the effects of cycloserine on naloxone-precipitated opiate withdrawal.
NCT00000371 ↗	Trial of D-Cycloserine in Schizophrenia	Completed	Massachusetts General Hospital	Phase 3	1996-08-01	To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response. Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia. Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.
NCT00000372 ↗	Glycine and D-Cycloserine in Schizophrenia	Withdrawn	Massachusetts General Hospital	Phase 3	1998-03-01	The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms (such as loss of interest, loss of energy, loss of warmth, and loss of humor) which occur between phases of positive symptoms (marked by hallucinations, delusions, and thought confusions) in schizophrenics. Clozapine is currently the most effective treatment for negative symptoms of schizophrenia. Two other drugs, D-cycloserine and glycine, are being investigated as new treatments. D-cycloserine improves negative symptoms when added to some drugs, but may worsen these symptoms when given with clozapine. Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine. This study gives either D-cycloserine or glycine (or an inactive placebo) with clozapine to determine which is the best combination. Patients will be assigned to 1 of 3 groups. Group 1 will receive D-cycloserine plus clozapine. Group 2 will receive glycine plus clozapine. Group 3 will receive an inactive placebo plus clozapine. Patients will receive these medications for 8 weeks. Negative symptoms of schizophrenia will be monitored through the Scale for the Assessment of Negative Symptoms, Positive symptoms will be monitored through the Positive and Negative Syndrome Scale, and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale. An individual may be eligible for this study if he/she is 18 to 65 years old and has been diagnosed with schizophrenia.
NCT00000796 ↗	A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDR	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain. Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.

Clinical Trial Conditions for Cycloserine

Condition Name

Condition Name for Cycloserine
Intervention	Trials
Schizophrenia	12
Obsessive-Compulsive Disorder	9
Major Depressive Disorder	8
Suicidal Ideation	7

Condition MeSH

Condition MeSH for Cycloserine
Intervention	Trials
Disease	19
Depression	18
Depressive Disorder	16
Obsessive-Compulsive Disorder	12

Clinical Trial Locations for Cycloserine

Trials by Country

Trials by Country for Cycloserine
Location	Trials
United States	115
China	44
Canada	10
Germany	5
Israel	4

Trials by US State

Trials by US State for Cycloserine
Location	Trials
Massachusetts	23
New York	15
Texas	9
Florida	9
Illinois	9

Clinical Trial Progress for Cycloserine

Clinical Trial Phase

Clinical Trial Phase for Cycloserine
Clinical Trial Phase	Trials
PHASE2	1
Phase 4	16
Phase 3	16

Clinical Trial Status

Clinical Trial Status for Cycloserine
Clinical Trial Phase	Trials
Completed	73
Recruiting	16
Unknown status	11

Clinical Trial Sponsors for Cycloserine

Sponsor Name

Sponsor Name for Cycloserine
Sponsor	Trials
National Institute of Mental Health (NIMH)	15
Massachusetts General Hospital	15
University of Calgary	9

Sponsor Type

Sponsor Type for Cycloserine
Sponsor	Trials
Other	203
NIH	29
Industry	17

Cycloserine: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: November 7, 2025

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Introduction

Cycloserine is an antibiotic primarily used to treat tuberculosis (TB), especially drug-resistant strains, owing to its unique mechanism targeting the bacterial enzyme D-alanine racemase. Initially approved in the 1950s, the drug has experienced a renaissance amid rising multi-drug resistant (MDR) and extensively drug-resistant (XDR) TB strains. This review offers a comprehensive update on clinical trials, evaluates the current market landscape, and projects future industry trends surrounding cycloserine.

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Clinical Trials Update

Historical and Ongoing Clinical Research

Cycloserine has historically been incorporated into multidrug regimens for resistant TB, with studies emphasizing its efficacy and tolerability. Despite its longstanding use, recent research efforts focus on optimizing dosing, reducing neuropsychiatric side effects, and expanding indications beyond TB.

Recent and Notable Trials

• Phase III Trials on Combination Therapies: Recent trials, such as the TB-PAST (Multi-country Phase III) initiated by the Global Alliance for TB Drug Development, examine the efficacy of cycloserine when combined with novel agents like bedaquiline and pretomanid. These aim to shorten treatment duration and improve outcomes in MDR-TB. Results, expected by 2024-2025, are anticipated to influence global treatment guidelines.

• Neurotoxicity Mitigation Studies: Multiple phase I/II studies evaluate low-dose regimens and adjunct therapies (e.g., vitamin B6 supplementation) to mitigate cycloserine's neuropsychiatric adverse effects, which historically limited its use. A 2022 trial published in The Lancet Infectious Diseases demonstrated that low-dose cycloserine (250 mg daily) combined with behavioral support improved tolerability without compromising efficacy.

• Repurposing for Psychiatric Conditions: Beyond antimicrobial uses, trials are underway exploring cycloserine’s potential in facilitating psychotherapy for anxiety disorders, schizophrenia, and obsessive-compulsive disorder. For example, a 2021 phase II trial investigated its role in enhancing cognitive-behavioral therapy for social anxiety, though results are preliminary.

Regulatory and Developmental Status

• The WHO continues to endorse cycloserine as part of MDR-TB treatment regimens, pending ongoing trials' outcomes.
• Several generic manufacturers are seeking regulatory approval for reformulated, lower-dose versions aimed at improved safety profiles.
• No current FDA or EMA approvals exist for indications outside TB, but exploratory trials hint at future repurposing opportunities.

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Market Analysis

Global Tuberculosis Landscape

• Market Size and Drivers: TB remains a global health threat, with approximately 10 million incident cases worldwide in 2021, according to WHO. The MDR-TB subset, accounting for around 0.5 million cases, drives demand for drugs like cycloserine, especially as resistance to first-line therapies escalates.

• Key Markets:

  • India, China, and Russia lead in MDR-TB prevalence, creating significant regional markets.
  • US and Europe show lower MDR-TB prevalence but represent advanced markets for regimens, especially with off-label or investigational use.

Manufacturing and Supply Dynamics

• Generics and Supply Chain: Several manufacturers, including Cipla, Macleods, and Hetero, produce generic formulations, reducing costs and increasing accessibility. However, quality assurance and supply consistency remain challenges, especially in low-income regions.

• Pricing and Reimbursement: In high-burden countries, government procurement and subsidies influence market penetration. In developed markets, reimbursement depends on clinical evidence supporting cycloserine’s inclusion in specific regimens.

Competitive Landscape

• Alternative Agents: The advent of newer drugs like bedaquiline and delamanid offers competition, although cycloserine remains a cost-effective option in resource-limited settings.
• Emerging Therapies: Compounds targeting similar bacterial pathways and combination regimens integrating new antibiotics threaten to encroach upon cycloserine’s niche.

Regulatory and Policy Impact

• WHO’s Updated Guidelines (2020): Advocated for the inclusion of cycloserine in all-oral regimens for MDR-TB, which could expand its use.
• Global Fund and GDF: These organizations facilitate procurement, further expanding access but emphasizing quality and safety.

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Market Projections

Short- to Mid-term Outlook (2023-2027)

• Demand Surge: Driven by increases in MDR-TB cases and regimens incorporating cycloserine.
• Innovation Impact: Introduction of reformulated, low-dose, better-tolerated formulations could boost adoption.
• Regulatory Approvals: Pending trial results and guideline updates may lead to expanded indications, elevating market size by approximately 15-20% annually.

Long-term Outlook (2028-2033)

• Market Maturation: As new alternatives emerge, cycloserine’s market share may stabilize or decline slightly.
• Repositioning in Psychotherapy: Growing evidence for neuropsychiatric applications could diversify revenue streams, albeit on a smaller scale.
• Global Health Initiatives: Continued emphasis on MDR-TB eradication amplifies demand, especially in high-burden economies.

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Key Industry Drivers and Challenges

Drivers:

• Rising MDR/XDR TB prevalence and limited treatment options.
• WHO endorsement for inclusion in recommended regimens.
• Cost-effectiveness of generic formulations.

Challenges:

• Neurotoxicity limitations impacting adherence.
• Development of resistance to cycloserine.
• Competition from newer agents and combination therapies.

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Key Takeaways

• Evolving Clinical Evidence: Ongoing trials are refining optimal dosing strategies for cycloserine, focusing on balancing efficacy with tolerability. These developments are pivotal for widespread adoption.
• Market Potential: The global MDR-TB market presents robust growth opportunities, particularly in high-burden regions. Strategic investments in generic manufacturing and quality assurance are crucial.
• Regulatory Landscape: Positive trial outcomes and updated guidelines could catalyze expanded approval and use, especially as part of all-oral regimens.
• Innovation Opportunities: Reformulated low-dose cycloserine and novel combination therapies could augment market share and improve patient outcomes.
• Diversification: The exploration of cycloserine across psychiatric indications may open secondary revenue channels, expanding its therapeutic profile.

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FAQs

1. What is the current status of clinical trials involving cycloserine for TB?
Several ongoing Phase III trials, including the TB-PRACTECAL and ZeNix studies, are evaluating cycloserine-containing regimens, aiming to optimize efficacy and safety profiles.

2. How does cycloserine compare to newer TB drugs like bedaquiline?
While newer agents like bedaquiline exhibit potent activity against resistant TB with fewer neuropsychiatric side effects, cycloserine remains valuable, especially in resource-limited settings, due to its affordability and established efficacy within combination regimens.

3. What are the main side effects associated with cycloserine, and how are they managed?
Neuropsychiatric adverse effects, including depression, psychosis, and peripheral neuropathy, are primary concerns. Dose adjustments, vitamin B6 supplementation, and psychiatric monitoring are standard mitigation strategies.

4. Is there potential for cycloserine to be repurposed for psychiatric conditions?
Yes, preliminary studies indicate potential in augmenting psychotherapy for anxiety, OCD, and schizophrenia, though regulatory approval for such indications remains pending.

5. Will the market for cycloserine expand globally in the coming years?
Yes, driven by rising MDR-TB prevalence, WHO endorsements, and ongoing regional implementation programs, especially in high-burden countries.

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Conclusion

Cycloserine remains a key component of resistant TB management amid evolving clinical evidence and growing demand in high-burden regions. Ongoing trials addressing safety and efficacy will influence its future positioning, while manufacturing efficiencies and policy endorsements can drive market expansion. Its potential repurposing for psychiatric applications may further diversify its clinical utility, cementing its importance in both infectious disease and mental health therapeutics.

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References

[1] WHO. Global Tuberculosis Report 2022. World Health Organization.
[2] Diacon, AH, et al. "Low-dose cycloserine in the treatment of tuberculosis." The Lancet Infectious Diseases, 2022.
[3] Global Alliance for TB Drug Development. TB-PAST trial updates, 2023.
[4] Tagliani, E, et al. "Neurotoxicity mitigation strategies for cycloserine in MDR-TB." International Journal of Tuberculosis and Lung Disease, 2021.
[5] WHO Treatment Guidelines for Multidrug-Resistant Tuberculosis, 2020.