Dextrin Sulfate as a Vaginal Microbicide: Randomized, Double-Blind, Placebo-Controlled Trial Including Healthy Female Volunteers and Their Male Partners

Abstract

Summary:This randomized, placebo-controlled trial assessed the safety and acceptability of vaginally administered 0.125% dextrin sulfate (DS) gel in sexually active women and their male partners. A single 2-mL dose of study gel was self-administered every night over two 14-day periods separated by a 7-day interval, during which menses was expected to occur. Up to two supplementary doses per 24 hours were provided for use before sexual intercourse. Semistructured interview, colposcopy, and laboratory safety studies were used to assess adverse events. Male partners who agreed to participate in a substudy were exposed to gel through sexual intercourse during the second 14-day exposure period. Seventy-three women (36 DS recipients and 37 placebo recipients) used at least one application of gel, of whom 66 (33 DS recipients and 33 placebo recipients) completed follow-up. Eleven women (5 DS recipients and 6 placebo recipients) reported intermenstrual bleeding during gel use, which in most cases was light and resolved within 24 hours. Ten male partners (4 with DS exposure and 6 with placebo exposure) were enrolled in the study and all completed follow-up. There was no evidence of systemic toxicity or genital epithelial disruption attributable to DS gel.

Naturally derived anti‐HIV agents

“…The experience with topically applied dextrin sulphate in human subjects (both male and female) shows that sulphated polysaccharides do not produce systemic toxicity or genital epithelial disruption (Low-Beer et al, 2002;Van Damme et al, 2002). Another sulphated polymannuroguluronate (SPMG), a marine sulphated polysaccharide extracted from brown algae with specific means of fractionation and chemical modification, has entered Phase II clinical trial in China as the first anti-AIDS drug candidate obtained from marine organisms (Miao et al, 2004).…”

A Dose-Ranging Phase I Study of Dextrin Sulphate, a Vaginal Microbicide, in HIV-Negative and HIV-Positive Female Volunteers

“…Three phase I clinical trials of DS gel have been completed involving 127 healthy female volunteers who received up to 0.125% DS or matched placebo. 11,12 These studies showed that DS at a concentration of 0.125% was safe and well tolerated. At that time, macaque challenge experiments also suggested a dose-dependent protective effect, and it was therefore decided to investigate higher doses of DS.…”

Biotechnological Engineering of Heparin/Heparan Sulphate: A Novel Area of Multi-Target Drug Discovery

“…On the other hand, the topic use of K5 derivatives can be envisaged. The importance of the development of an efficacious vaginal microbicide has been raised [84] and different polyanions [85][86][87], including K5 derivatives [13], have been proposed for this use. Alternatively, K5 derivatives may be employed for intralesional administration, as it may be the case for Kaposi's sarcoma [65] where both FGF2 and Tat protein are involved [88].…”