American Society of Hirudotherapy

Effects of leech therapy on knee osteoarthritis: a randomized clinical trial in an Iranian population

Khoshnevisan A, Sahebkar A, Mohammadpour AH, Mosaffa-Jahromi M (2022) · Journal of Traditional and Complementary Medicine · n=80

RCT evidence detailTrial reference
GRADE LowCohort / case seriesCondition: Knee Osteoarthritis
Sample size of this trial compared with other Knee Osteoarthritis trialsWang H 2018264Lauche R 2025240Lauche R 2014237Farzali S 2025181Cui Y 2024144Andereya S 2008113Andereya S 2008113Sarbaev IS 201996Isik M 201790Khoshnevisan A 202280
This trial (highlighted) by sample size alongside other indexed Knee Osteoarthritis trials. Larger trials generally carry more statistical weight.

Study Profile

Design
single-center, open-label, randomized controlled trial (Mashhad)
Sample size (n)
80
Intervention
Two sessions of 4-6 Hirudo medicinalis leeches, 21 days apart, periarticular knee application
Comparator
Naproxen 500mg twice daily for 6 weeks plus standard knee exercises
Primary endpoint
WOMAC composite score at week 6
Primary result
WOMAC composite reduction 41.2 points in leech vs 23.8 in naproxen at week 6 (between-group difference 17.4 points, p<0.001); effect maintained at week 12
Effect size (Cohen's d)
0.89
Follow-up duration
12 weeks

Key Findings

  • First Iranian RCT for hirudotherapy in knee OA — adds non-European, non-North-American data
  • Compared against oral NSAID (naproxen) rather than topical — more rigorous comparator
  • Effect size consistent with German trials despite different patient population (Iranian, more rural)
  • Inflammation markers (CRP, IL-6) reduced significantly in leech arm — first inflammatory-biomarker RCT data
  • No serious adverse events; mild local pruritus in 22% of leech patients

Limitations

  • Single center, Iran — local Persian medicine context may bias patient expectations
  • Open-label
  • No assessor blinding for WOMAC
  • 6-week comparator phase may underestimate naproxen's sustained effect
  • Biomarker findings exploratory — not powered as primary endpoint

Clinical Implications

Khoshnevisan 2022 extends the knee OA evidence base outside the German/European tradition for the first time at the RCT level. Comparing against oral NSAIDs (the global standard) rather than topical diclofenac strengthens the clinical applicability. The exploratory CRP/IL-6 biomarker data provide preliminary mechanistic confirmation of the anti-inflammatory hypothesis. For US clinicians, this trial adds important external generalizability.

Related Trials

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.