Advertisement

Drugs in R & D

, Volume 5, Issue 2, pp 63–71 | Cite as

Improvement of Cutaneous Microcirculation and Oxygen Supply in Patients with Chronic Venous Insufficiency by Orally Administered Extract of Red Vine Leaves AS 195

A Randomised, Double-Blind, Placebo-Controlled, Crossover Study
  • Ulrich Kalus
  • Juergen Koscielny
  • Alexandre Grigorov
  • Eckhard Schaefer
  • Hubertus Peil
  • Holger Kiesewetter
Original Research Article

Abstract

Objective

To investigate the effect of the red vine leaf extract AS 195 on cutaneous microvascular blood flow, transcutaneous oxygen pressure (tcpO2), and leg oedema in patients with chronic venous insufficiency (CVI).

Design and patients

The study was a randomised, double-blind, placebo-controlled, crossover trial for which 129 men and women, aged ≥18 years, with CVI stage I or II were screened. Seventy-one fulfilled the inclusion criteria and were randomised.

Interventions

A total of 71 patients were divided into two groups. The first group (n=36) received AS 195 360mg once daily during a first 6-week treatment period, followed by a 4-week placebo washout period and then placebo during the second 6-week treatment period. The second group (n=35) started with placebo and received AS 195 360mg after the placebo washout. The cutaneous microvascular blood flow in the malleolar region was measured using a newly developed laser Doppler device. TcpO2 was measured using a solid-state electrode.

Results

After 6 weeks, patients in the AS 195 group had increased microvascular blood flow values (+241.8±18.7 arbitrary units [AU] versus a decrease of −41.0±18.7AU in the placebo group; p < 0.0001). Oxygen increased to 1.35±0.97mm Hg (placebo: decrease of −7.27±0.97mm Hg; p < 0.0001). After 6 weeks of treatment the leg circumference was decreased (ankle level: by −0.39±0.09cm versus +0.29±0.09cm; p < 0.0001; calf level: by −0.54±0.05cm versus +0.14±0.05cm; p < 0.0001).

Conclusion

The administration of AS 195 improved objective symptoms of CVI and may prevent CVI deterioration.

Keywords

Hesperidin Isoquercitrin Microvascular Blood Flow Chronic Venous Insufficiency Chronic Venous Insufficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was funded by Boehringer Ingelheim, Ingelheim am Rhein, Germany. Holger Kiesewetter was the principal investigator and recruited the patients. He contributed to the design and coordinated the study. Day-to-day conduct of the study, record keeping, and assessment of patients was the responsibility of UK, JK and AG. Overall analysis of data and statistical analysis was the responsibility of HP. ES and HP set up the trial protocol and the paper. All authors reviewed both documents and approved the final version.

The clinical investigations were in compliance with the current relevant German laws. HK has a consultancy agreement with the sponsor. ES and HP are employees of the sponsor.

References

  1. 1.
    Van den Oever R, Hepp B, Debbaut B, et al. Socio-economic impact of chronic venous insufficiency: an underestimated public health problem. Int Angiol 1998; 17 (3): 161–7PubMedGoogle Scholar
  2. 2.
    Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology 2001; 52 Suppl. 1: S5–15PubMedCrossRefGoogle Scholar
  3. 3.
    Frick RW. Three treatments for chronic venous insufficiency: escin, hydroxyethylrutoside, and Daflon. Angiology 2000; 51 (3): 197–205PubMedCrossRefGoogle Scholar
  4. 4.
    Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I–II): a randomized, double-blind, placebo-controlled trial. Arzneimittel Forschung 2000; 50 (2): 109–17PubMedGoogle Scholar
  5. 5.
    Antignani PL. Classification of chronic venous insufficiency: a review. Angiology 2001; 52 Suppl. 1: S17–26PubMedCrossRefGoogle Scholar
  6. 6.
    Doerschel K, Müller GJ. PC-integrated laser doppler blood flow measurements in skin In: Farkas DL, Leif RC, Priezzhev AV, et al., editors. Proceedings of the International Society for Optical Engineering (SPIE) 1996; 2678: 382–8Google Scholar
  7. 7.
    Fagrell B. Advances in microcirculation network evaluation: an update. Int J Microcirc Clin Exp 1995; 15 Suppl. 1: S34–40CrossRefGoogle Scholar
  8. 8.
    Bollinger A, Jager K, Juenger M, et al. The vascular laboratory: advances in noninvasive techniques. World J Surg 1988; 12 (6): 724–31PubMedCrossRefGoogle Scholar
  9. 9.
    Diehm C, Trampisch HJ, Lange S, et al. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet 1996; 347 (8997): 292–4PubMedCrossRefGoogle Scholar
  10. 10.
    Struckmann JR. Clinical efficacy of micronized purified flavonoid fraction: an overview. J Vasc Res 1999; 36 Suppl. 1: S37–41CrossRefGoogle Scholar
  11. 11.
    Ramelet AA. Clinical benefits of Daflon 500mg in the most severe stages of chronic venous insufficiency. Angiology 2001; 52 Suppl. 1: S49–56PubMedCrossRefGoogle Scholar
  12. 12.
    Bergan JJ, Schmid-Schoenbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500mg. Angiology 2001; 52 Suppl. 1: S43–7PubMedCrossRefGoogle Scholar
  13. 13.
    Signorelli SS, Malaponte MG, Di Pino L, et al. Venous stasis causes release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) by monocyte-macrophage. Clin Hemorheol Microcirc 2000; 22 (4): 311–6PubMedGoogle Scholar
  14. 14.
    Coleridge Smith PD. Update on chronic-venous-insufficiency-induced inflammatory processes. Angiology 2001; 52 Suppl. 1: S35–42CrossRefGoogle Scholar
  15. 15.
    Schmid-Schoenbein GW, Takase S, Bergan JJ. New advances in the understanding of the pathophysiology of chronic venous insufficiency. Angiology 2001; 52 Suppl. 1: S27–34CrossRefGoogle Scholar
  16. 16.
    Nees S, Weiss DR, Reichenbach-Klinke E, et al. Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro. Arzneimittel Forschung 2003; 53 (5): 330–41PubMedGoogle Scholar
  17. 17.
    Bollinger A, Leu AJ, Hoffmann U, et al. Microvascular changes in venous disease: an update. Angiology 1997; 48 (1): 27–32PubMedCrossRefGoogle Scholar
  18. 18.
    Tulevski II, Ubbink DT, Jacobs MJ. Red and green laser Doppler compared with capillary microscopy to assess skin microcirculation in the feet of healthy subjects. Microvasc Res 1999; 58 (2): 83–8PubMedCrossRefGoogle Scholar
  19. 19.
    Cesarone MR, De Sanctis MT, Incandela L, et al. Methods of evaluation and quantification of microangiopathy in high perfusion microangiopathy (chronic venous insufficiency and diabetic microangiopathy). Angiology 2001; 52 Suppl. 2: S3–7PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Ulrich Kalus
    • 1
  • Juergen Koscielny
    • 1
  • Alexandre Grigorov
    • 1
  • Eckhard Schaefer
    • 2
  • Hubertus Peil
    • 3
  • Holger Kiesewetter
    • 1
  1. 1.Institute for Transfusion MedicineUniversity Clinic CharitéBerlinGermany
  2. 2.Consumer Health CareBoehringer Ingelheim GmbHIngelheim am RheinGermany
  3. 3.Medical Data ServicesBoehringer Ingelheim Pharma GmbH&Co KGIngelheim am RheinGermany

Personalised recommendations