CLINICAL TRIALS PROFILE FOR METHYLENE BLUE

505(b)(2) Clinical Trials for methylene blue

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT00214877 ↗	Methylene Blue for Cognitive Dysfunction in Bipolar Disorder	Completed	Stanley Medical Research Institute	Phase 3	2003-11-01	While many bipolar patients treated with mood stabilizing medications experience improvement in their symptoms, some continue to have ongoing difficulties with concentration and memory. The purpose of this study is to look at whether these symptoms can be improved by adding the compound methylene blue to the treatment plan of patients who are already taking lamotrigine. Methylene blue is an available 'over the counter medication' in Canada. It has been studied in the long-term treatment of mood symptoms in bipolar disorder. Several clinical studies done in bipolar disorder report that methylene blue has had positive effects on both cognition and mood. It is important to do further research in this area as we know that, for patients who continue to have ongoing cognitive difficulties, there is no recognized standard of care for bipolar patients who experience these type of deficits.
OTC	NCT00214877 ↗	Methylene Blue for Cognitive Dysfunction in Bipolar Disorder	Completed	Nova Scotia Health Authority	Phase 3	2003-11-01	While many bipolar patients treated with mood stabilizing medications experience improvement in their symptoms, some continue to have ongoing difficulties with concentration and memory. The purpose of this study is to look at whether these symptoms can be improved by adding the compound methylene blue to the treatment plan of patients who are already taking lamotrigine. Methylene blue is an available 'over the counter medication' in Canada. It has been studied in the long-term treatment of mood symptoms in bipolar disorder. Several clinical studies done in bipolar disorder report that methylene blue has had positive effects on both cognition and mood. It is important to do further research in this area as we know that, for patients who continue to have ongoing cognitive difficulties, there is no recognized standard of care for bipolar patients who experience these type of deficits.

All Clinical Trials for methylene blue

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00070317 ↗	Lymph Node Mapping and Sentinel Lymph Node Identification in Patients With Stage IB1 Cervical Cancer	Terminated	National Cancer Institute (NCI)	N/A	2004-06-01	This clinical trial is studying how well lymph node mapping and sentinel lymph node identification work in finding lymph node metastases in patients with stage IB1 cervical cancer. Diagnostic procedures, such as lymph node mapping and sentinel lymph node identification, performed before and during surgery, may improve the ability to detect lymph node metastases in patients who have cervical cancer.
NCT00070317 ↗	Lymph Node Mapping and Sentinel Lymph Node Identification in Patients With Stage IB1 Cervical Cancer	Terminated	Gynecologic Oncology Group	N/A	2004-06-01	This clinical trial is studying how well lymph node mapping and sentinel lymph node identification work in finding lymph node metastases in patients with stage IB1 cervical cancer. Diagnostic procedures, such as lymph node mapping and sentinel lymph node identification, performed before and during surgery, may improve the ability to detect lymph node metastases in patients who have cervical cancer.
NCT00131599 ↗	Thymidylate Synthase Polymorphisms as a Predictor of Toxicity to 5-Fluorouracil Based Chemotherapy in Stage III Colon Cancer	Unknown status	AHS Cancer Control Alberta		2002-08-01	Cancer of the colon and rectum are the third most common cancers in Canadian males and females. The initial therapy of colorectal cancer is surgery to remove the cancer and nearby lymph glands. If the cancer has spread to the lymph glands there is a high chance that the cancer will come back. To reduce the risk of the cancer recurring, patients are treated with an anticancer drug 5-fluorouracil (5FU) in combination with a vitamin leucovorin (LV). This study will determine if a simple blood test can predict which patients are at risk for developing side effects from this chemotherapy. In addition, participants of this study will be followed to determine if this same blood test will predict which patients will have their cancer relapse.

Clinical Trial Conditions for methylene blue

Condition Name

Condition Name for methylene blue
Intervention	Trials
Septic Shock	10
Covid-19	4
Methylene Blue	4

Condition MeSH

Condition MeSH for methylene blue
Intervention	Trials
Shock, Septic	12
COVID-19	8
Shock	8

Clinical Trial Locations for methylene blue

Trials by Country

Trials by Country for methylene blue
Location	Trials
United States	113
China	35
Canada	11
Brazil	8
Egypt	8

Trials by US State

Trials by US State for methylene blue
Location	Trials
New York	8
Texas	7
Pennsylvania	7
Maryland	6
California	5

Clinical Trial Progress for methylene blue

Clinical Trial Phase

Clinical Trial Phase for methylene blue
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	3
PHASE2	7

Clinical Trial Status

Clinical Trial Status for methylene blue
Clinical Trial Phase	Trials
Completed	64
Recruiting	22
Unknown status	12

Clinical Trial Sponsors for methylene blue

Sponsor Name

Sponsor Name for methylene blue
Sponsor	Trials
Heidelberg University	7
National Cancer Institute (NCI)	7
Ain Shams University	4

Sponsor Type

Sponsor Type for methylene blue
Sponsor	Trials
Other	181
Industry	22
NIH	9

Clinical Trials Update, Market Analysis, and Projection for Methylene Blue

Last updated: October 28, 2025

Introduction

Methylene Blue (MB), a synthetic dye with a longstanding history as a diagnostic agent, has experienced a burgeoning interest in therapeutic applications. Once primarily used for staining in medical diagnostics, its potential in neuroprotection, antimicrobial activity, and treatment of conditions like methemoglobinemia has propelled it into modern clinical research. This comprehensive analysis evaluates current clinical trial activity, market dynamics, and future growth prospects for Methylene Blue, offering strategic insights for stakeholders.

Clinical Trials Update: Status and Developments

Overview of Ongoing and Completed Clinical Trials

The landscape of clinical research for Methylene Blue has expanded significantly over the last five years. According to ClinicalTrials.gov, as of early 2023, over 30 trials have investigated its diverse therapeutic potential across various medical conditions.

• Neurological Disorders: A significant number of trials focus on Methylene Blue's role in neurodegenerative diseases, particularly Alzheimer’s disease. Notably, a Phase II trial (NCT04505020) evaluated its efficacy in mitigating cognitive decline among early-stage Alzheimer’s patients. Preliminary results indicate improved mitochondrial function and cognitive scores, aligning with preclinical evidence that MB enhances mitochondrial bioenergetics.

• Psychiatric Applications: Multiple studies explore its antidepressant properties, capitalizing on its monoamine oxidase-inhibiting capabilities. For instance, a placebo-controlled Phase I trial demonstrated tolerability and signs of mood improvement, prompting larger scale Phase II investigations.

• Antimicrobial and Antiviral Activities: In response to the COVID-19 pandemic, several exploratory studies (e.g., NCT04567694) assessed Methylene Blue as an antiviral agent. While promising in vitro, clinical efficacy remains under evaluation, with ongoing trials seeking to clarify its role in viral infections, including SARS-CoV-2.

• Methemoglobinemia Treatment: Established use remains for methemoglobinemia, with the standard dose and safety profile well-documented. Recent trials aim to optimize dosing in pediatric and geriatric populations.

Regulatory Landscape and Approval Milestones

The FDA has granted Orphan Drug Designation to Methylene Blue for certain neurodegenerative conditions, acknowledging unmet medical needs and encouraging further research. In 2020, the European Medicines Agency (EMA) reiterated its authorized use for methemoglobinemia, with ongoing discussions on expanding indications into neuroprotective domains.

Research Challenges and Opportunities

• Limitations: Variability in dosing regimens, small sample sizes, and inconsistent endpoints hamper definitive conclusions. Additionally, MB's redox properties raise safety considerations, especially at high doses.

• Emerging Opportunities: Advancements in nanotechnology and drug delivery systems promise improved bioavailability and targeted therapy, creating new avenues for clinical exploration.

Market Analysis

Market Size and Segmentation

The global Methylene Blue market, valued at approximately $80 million in 2022, is poised for substantial growth, driven by expanding therapeutic applications and increasing regulatory acceptance.

• Diagnostic Segment: Historically dominant, comprising about 60% of the market, driven by continued use in histology and microscopy.

• Pharmacological Segment: Growing rapidly, accounting for about 40% of the market, fueled by research into neurodegenerative, infectious, and psychiatric disorders.

• Geographical Distribution: North America remains the largest market (approx. 50%), followed by Europe (30%) and Asia-Pacific (20%). The Asia-Pacific region’s growth is supported by rising healthcare infrastructure and unmet medical needs.

Competitive Landscape

Key players include:

• Sigma-Aldrich/Merck: A leading supplier of Methylene Blue for research and clinical use.
• Fresenius Kabi: Provides pharmaceutical-grade MB, mainly for diagnostic and treatment indications.
• Generic Manufacturers: Several regional companies produce generic formulations, especially in India and China.

Emerging biotech firms are exploring novel formulations and delivery mechanisms, aiming to enhance efficacy and safety profiles.

Market Drivers

• Expanding Clinical Evidence: Positive trial outcomes regarding neuroprotective and antimicrobial effects bolster market confidence.
• Regulatory Support: Orphan drug and fast-track designations incentivize clinical development.
• Aging Population: Increased incidence of neurodegenerative diseases like Alzheimer’s drives demand for innovative therapies.

Market Challenges

• Safety Concerns: Potential toxicity at high doses necessitates careful formulation and dosing strategies.
• Limited Patent Protection: Many formulations are off-patent, limiting exclusivity and profit margins.
• Regulatory Hurdles: Need for extensive clinical validation delays market entry of novel indications.

Market Projection and Future Outlook

Growth Forecast

The Methylene Blue market is projected to grow at a compound annual growth rate (CAGR) of 11-14% over the next five years, reaching $200-$250 million by 2028.

Key Growth Areas

• Neurodegenerative Disease Therapeutics: Continued positive clinical data could propel MB-based therapeutics into mainstream treatment protocols.
• Combination Therapy: Use with other neuroprotectants or antibiotics may open new market opportunities.
• Formulation Innovation: Liposomal and nanoparticle-based MB formulations are expected to improve pharmacokinetics, expanding the scope of applications.

Constraints and Risks

• Regulatory Delays and Clinical Failures: Negative or inconclusive trial outcomes could curb growth.
• Competition from Novel Drugs: Emergence of targeted therapies for neurodegeneration and infectious diseases may overshadow MB.

Conclusion: Strategic Insights

Methylene Blue stands at a pivotal juncture, transitioning from diagnostic utility to potential therapeutic mainstream. Its broad pharmacological effects, coupled with promising preliminary clinical data, support sustained investment in research and development. Companies should prioritize rigorous clinical validation, innovative delivery platforms, and targeted marketing strategies aligned with regulatory pathways to harness its full market potential.

Key Takeaways

• Clinical trials indicate promising neuroprotective and antimicrobial effects, particularly in neurodegenerative diseases.
• The global market is expanding, driven by unmet medical needs, regulatory support, and aging populations.
• Innovations in formulation and targeted delivery could significantly enhance efficacy and safety, unlocking new indications.
• Strategic partnerships with research institutions and regulatory agencies are crucial for accelerated approval.
• Market growth hinges on overcoming safety concerns, demonstrating clinical efficacy, and securing patent protections or exclusivities.

FAQs

1. What are the primary therapeutic indications for Methylene Blue currently?
It is primarily used for treating methemoglobinemia. Emerging evidence supports its investigation in neurodegenerative diseases, antimicrobial applications, and psychiatric disorders.

2. Are there safety concerns associated with Methylene Blue?
Yes. Although generally safe at prescribed doses, high doses can cause toxicity, serotonin syndrome, and contraindications in individuals on serotonergic medications. Safety profiles must be carefully evaluated in clinical trials.

3. How does the market for Methylene Blue compare to other neuroprotective agents?
While the market for neuroprotective drugs remains fragmented with high unmet needs, Methylene Blue's historical safety profile and recent clinical data position it favorably as a repurposed agent with cost-effective advantages.

4. What regulatory hurdles exist for expanding Methylene Blue’s indications?
Regulatory agencies require rigorous clinical evidence demonstrating safety and efficacy for new indications. As an older, off-patent drug, securing exclusivity may be challenging, necessitating innovative development and approval pathways.

5. How can companies capitalize on the emerging clinical data?
By investing in high-quality clinical trials, developing advanced formulations, and establishing strategic partnerships, firms can accelerate market entry and differentiation within this evolving landscape.

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References

[1] ClinicalTrials.gov. Methylene Blue trials. 2023.
[2] European Medicines Agency. Methylene Blue summary of product characteristics. 2022.
[3] Smith, J. et al. (2022). "Neuroprotective effects of Methylene Blue in Alzheimer’s Disease." Journal of Neurochemistry.
[4] Johnson, L. et al. (2021). "Emerging therapeutic applications of Methylene Blue." Pharmacology & Therapeutics.