Division of Basic and Translational Sciences
We are seeking Concept Clearance for a Request for Project (RFP) to assess the efficacy and safety of a novel topical thalidomide formulation for healing of aphthous ulcers associated with HIV/AIDS.
Infection with HIV results in progressive immune dysfunction characterized by opportunistic infections, malignancies, impaired wound healing, and idiopathic cutaneous and mucosal lesions. The oral cavity is a common site for these mucosal lesions. Studies of prevalence in clinical populations report aphthous ulceration in 15 to 31 percent of HIV-infected patients. Hence, recurrent aphthous ulcers are a frequent oral manifestation in HIV-infected patients, causing substantial morbidity in the form of oral pain. Oral pain leads to a decrease in food intake and associated weight loss, as well as diminished quality of life. There are no satisfactory therapies or accepted standards of care associated with aphthous ulceration in HIV seropositive (+) patients.
Thalidomide given PO is effective for aphthous ulcers in HIV+ as well as immunocompetent patients. However, its utility has been limited by its spectrum of adverse effects. The combination of lack of tolerability for PO thalidomide, its teratogenicity, and reported increases in viral load, have raised concerns regarding use of this drug in HIV-infected patients. Given the growing numbers of patients with HIV infection and the absence of other effective treatments for these painful and debilitating ulcerations, the need exists to develop alternative treatment strategies. Topical drug administration is a strategy for enhancing absorption at the anatomical target site while lowering plasma drug concentrations, hence decreasing the potential for toxicity.
When given PO, thalidomide takes four to six weeks to reach sufficient tissue concentrations to promote ulcer healing. However, results from a pilot clinical trial have demonstrated efficacy for healing and pain reduction for a 20 mg topical thalidomide in a mean of 17 days, with minimal systemic absorption and adverse effects. This suggests that topical administration produces high local tissue concentrations which cannot be achieved with PO administration without dose-limiting adverse effects. Topical thalidomide may be an effective alternative to PO thalidomide treatment for aphthous ulcers in patients with HIV infection, without the side effect liability.
This multi-center clinical trial will test topical thalidomide for lesion healing and diminution of pain as well as toxicity.