CLINICAL TRIALS PROFILE FOR CYCLOSERINE

All Clinical Trials for CYCLOSERINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000372 ↗	Glycine and D-Cycloserine in Schizophrenia	Withdrawn	Massachusetts General Hospital	Phase 3	1998-03-01	The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative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.
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.
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.

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	17
Depressive Disorder	16
Compulsive Personality Disorder	12

Clinical Trial Locations for CYCLOSERINE

Trials by Country

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Trials by Country for CYCLOSERINE
Location	Trials
United States	114
China	44
Canada	10
Germany	5
Israel	4

Trials by US State

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−

Trials by US State for CYCLOSERINE
Location	Trials
Massachusetts	23
New York	15
Texas	9
Illinois	9
Florida	8

Clinical Trial Progress for CYCLOSERINE

Clinical Trial Phase

Clinical Trial Phase for CYCLOSERINE
Clinical Trial Phase	Trials
Phase 4	16
Phase 3	16
Phase 2/Phase 3	10

Clinical Trial Status

Clinical Trial Status for CYCLOSERINE
Clinical Trial Phase	Trials
Completed	73
Recruiting	15
Unknown status	11

Clinical Trial Sponsors for CYCLOSERINE

Sponsor Name

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

Sponsor Type

Sponsor Type for CYCLOSERINE
Sponsor	Trials
Other	201
NIH	29
Industry	16

Cycloserine: Clinical Trials, Market Analysis, and Projections

Introduction

Cycloserine, a broad-spectrum antibiotic and analog of the amino acid D-alanine, has been in use for decades, primarily in the treatment of tuberculosis and certain urinary tract infections. However, recent clinical trials and market analyses reveal its potential in other therapeutic areas and significant market growth.

Clinical Trials Update

Cycloserine in Major Depressive Disorder (MDD)

A recent clinical trial published in 2022 explored the efficacy of adjunctive D-cycloserine in enhancing transcranial magnetic stimulation (TMS) treatment outcomes for Major Depressive Disorder (MDD). This double-blind, placebo-controlled trial involved 50 participants and showed promising results. The group receiving iTBS (intermittent theta-burst stimulation) plus D-cycloserine had greater improvements in MADRS scores and higher rates of clinical response and remission compared to the iTBS plus placebo group[1].

Cycloserine in Cognitive-Behavioral Therapy (CBT) for Panic Disorder

Another clinical trial investigated the effect of a single dose of D-cycloserine on the efficacy of cognitive-behavioral therapy (CBT) for panic disorder. This randomized placebo-controlled trial found that the combination of CBT with D-cycloserine led to a greater reduction in threat bias on the day after treatment, suggesting a potential cognitive enhancer role for D-cycloserine in CBT[4].

Cycloserine in Chronic Pain and Bipolar Depression

NRx Pharmaceuticals is conducting trials on NRX-101, a combination of D-cycloserine and lurasidone, targeting chronic pain and bipolar depression. The FDA has issued a "Study May Proceed" letter, allowing NRx to proceed with pharmacokinetic studies for chronic pain treatment. This development aligns with previous preclinical requirements for bipolar depression and indicates potential future registrational trials[3].

Mechanism of Action

Cycloserine works by interfering with bacterial cell wall synthesis through competitive inhibition of enzymes such as L-alanine racemase and D-alanylalanine synthetase. In addition, it acts as an inhibitor of the N-methyl-D-aspartate (NMDA) glutamate receptor, which is relevant in its potential therapeutic applications beyond antibacterial use[5].

Market Analysis

Current Market Size and Forecast

The market for cyclosporine (a different but similarly named drug) is often confused with cycloserine, but the focus here is on cycloserine's niche markets. However, the broader context of immunosuppressants and antibiotics can provide insights. The cyclosporine market, for example, was valued at $2.99 billion in 2024 and is projected to reach $8.26 billion by 2031, growing at a CAGR of 14.96%[2].

Potential Market Growth for Cycloserine

While specific market data for cycloserine is limited due to its niche use, the drug's potential in new therapeutic areas such as MDD, CBT enhancement, and chronic pain could significantly expand its market. The success of clinical trials and regulatory approvals will be crucial in determining its future market size.

Geographic Distribution

The global market for antibiotics and immunosuppressants is segmented geographically, with regions like the Asia Pacific expected to show significant growth due to improving healthcare infrastructure and increasing patient awareness. Similar trends could apply to cycloserine if it gains broader therapeutic use[2].

Key Players and Competitive Landscape

Currently, the market for cycloserine is not as competitive as that for cyclosporine, which involves major players like Shire, Otsuka, Alcon, and Novartis. However, companies like NRx Pharmaceuticals are emerging with new formulations and indications that could change the competitive landscape for cycloserine[2][3].

Applications and Segmentation

Traditional Use in Tuberculosis and UTIs

Cycloserine is traditionally used in the treatment of tuberculosis and certain urinary tract infections. Its efficacy in these areas remains a cornerstone of its market presence[5].

Emerging Therapeutic Areas

• Major Depressive Disorder (MDD): The adjunctive use of D-cycloserine with TMS shows promise in enhancing treatment outcomes for MDD.
• Cognitive-Behavioral Therapy (CBT): D-cycloserine's role as a cognitive enhancer in CBT for panic disorder and other conditions is being explored.
• Chronic Pain and Bipolar Depression: NRX-101, a combination of D-cycloserine and lurasidone, is under investigation for these indications[1][3][4].

Challenges and Limitations

Side Effects and Safety

Cycloserine can have side effects such as kidney problems, high blood pressure, gum disease, tremors, and increased hair growth. These adverse effects need careful management and monitoring[2].

Regulatory Approvals

The progression of cycloserine into new therapeutic areas depends on regulatory approvals and the outcomes of ongoing clinical trials. Positive results and favorable regulatory decisions are crucial for market expansion[3].

Key Takeaways

• Cycloserine shows promise in enhancing TMS treatment for MDD and as a cognitive enhancer in CBT.
• Ongoing trials for chronic pain and bipolar depression could expand its therapeutic use.
• The drug's traditional use in tuberculosis and UTIs remains significant.
• Market growth potential is high if new indications are successfully approved.
• Regulatory approvals and clinical trial outcomes are critical for future market expansion.

FAQs

What is the traditional use of cycloserine?

Cycloserine is traditionally used in the treatment of tuberculosis and certain urinary tract infections.

How is cycloserine being explored in new therapeutic areas?

Cycloserine is being explored as an adjunct to TMS for Major Depressive Disorder, as a cognitive enhancer in CBT for panic disorder, and in combination with lurasidone for chronic pain and bipolar depression.

What are the potential side effects of cycloserine?

Cycloserine can cause side effects such as kidney problems, high blood pressure, gum disease, tremors, and increased hair growth.

Which companies are involved in the development of new cycloserine formulations?

Companies like NRx Pharmaceuticals are involved in the development of new formulations and indications for cycloserine.

What is the current market outlook for cycloserine?

While specific market data for cycloserine is limited, its potential in new therapeutic areas suggests significant market growth if clinical trials and regulatory approvals are successful.

Sources

1. Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Treatment-Resistant Depression: A Randomized Clinical Trial. PubMed, 2022.
2. Cyclosporine Market Size, Share, Trends & Forecast. Verified Market Research.
3. NRx Pharmaceuticals Announces Further Alignment with FDA on Initiation of Registrational Trials for NRX-101 in the Treatment of Chronic Pain. BioSpace, 2023.
4. Clinical Trial Results: The effect of a single-dose of d-cycloserine on the basic effects of cognitive-behaviour therapy for panic disorder. Clinical Trials Register.
5. Cycloserine: Uses, Interactions, Mechanism of Action. DrugBank.