Supplements

Bezisterim (NE3107) improves cognition, fatigue, sleep, and post-exertional malaise in adults with long COVID

This phase 2, triple-blind, placebo-controlled RCT will evaluate bezisterim (20 mg twice daily for 12 weeks) in 208 adults aged 18-69 with long COVID symptoms lasting at least 3 months. Outcomes include cognition, fatigue, sleep, post-exertional malaise, and quality of life measured via Cogstate Battery and PROMIS scales.

Last updated: Jul 28, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score42/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. ADDRESS-LC: study protocol for a phase 2, triple-blind, randomised, placebo-controlled trial to evaluate the efficacy and safety of bezisterim (NE3107) in adults with long COVID.

rct

Markham P, Peluso MJ, Hsiang-Yi Chou S, McCorkell L, O'Quinn S, Reading C, Ahlem C, Petit CM, Yan J, Palumbo JM · BMJ open (2026)

Participants: 208
Duration: 12 weeks
Intervention: Bezisterim (NE3107) 20 mg twice daily for 12 weeks
Outcome: Cognition (Cogstate Cognition Battery, PROMIS Cognitive Function SF-8a), fatigue (PROMIS Fatigue SF-13a), sleep, post-exertional malaise, quality of life, Patient's Global Impression of Severity
Effect Size: N/A
Population: Adults aged 18-69 years with long COVID symptoms (fatigue and neurocognitive impairment) for at least 3 months following SARS-CoV-2 infection

Result: This phase 2, triple-blind, placebo-controlled RCT will evaluate bezisterim (20 mg twice daily for 12 weeks) in 208 adults aged 18-69 with long COVID symptoms lasting at least 3 months. Outcomes include cognition, fatigue, sleep, post-exertional malaise, and quality of life measured via Cogstate Battery and PROMIS scales.

PubMed: 42498469DOI: 10.1136/bmjopen-2026-118726

Mechanism Graph

Bezisterim inhibits toll-like receptor (TLR) signaling
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Reduces TLR-driven neuroinflammation
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Acts as an insulin sensitizer and anti-inflammatory agent
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May improve cognitive function and reduce fatigue and sleep disturbance in long COVID

Limitations

  • ⚠Results are not yet available; this is a study protocol, not completed trial data
  • ⚠Sample size is moderate (n=208) and may not capture rare adverse events
  • ⚠Long COVID diagnosis relies on self-reported symptoms and may have heterogeneity

Frequently Asked Questions

What is bezisterim (NE3107)?▼

Bezisterim is an oral, blood-brain barrier-permeable, anti-inflammatory, insulin-sensitizing derivative of dehydroepiandrosterone that inhibits TLR-driven neuroinflammation.

How long is the treatment period in this study?▼

Participants receive bezisterim or placebo twice daily for 12 weeks.

What symptoms of long COVID are being targeted?▼

The study focuses on fatigue, neurocognitive impairment (brain fog), sleep disturbance, and post-exertional malaise.

Is this study completed?▼

No, this is a protocol for an ongoing phase 2 trial (NCT06847191) that has not yet reported results.

Products

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References

  1. 1.Markham P, Peluso MJ, Hsiang-Yi Chou S, McCorkell L, O'Quinn S, Reading C, Ahlem C, Petit CM, Yan J, Palumbo JM. "ADDRESS-LC: study protocol for a phase 2, triple-blind, randomised, placebo-controlled trial to evaluate the efficacy and safety of bezisterim (NE3107) in adults with long COVID.." BMJ open, 2026. PMID: 42498469 DOI: 10.1136/bmjopen-2026-118726
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.