Clinical trial NCT00598871
Conditions: Diabetes
Keywords: Thymosin beta 4 Corneal wound healing Vitrectomy Diabetes
Sponsor: ReGenTree, LLC
Start date: 2007-12-01; Completion date: 2009-02-01
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
As a consequence of damage to multiple organ systems throughout the course of their disease, diabetic patients suffer a number of chronic complications giving rise to increased morbidity, mortality, and health care costs specific to this population. Within the ophthalmic domain, diabetic retinopathy (DR) frequently induces serious visual impairment. Although DR can be addressed surgically, surgery remains a less than ideal intervention within this population with a well-characterized compromised ability to heal. The introduction of a therapeutic agent that could accelerate wound closure and decrease healing time, thereby reducing the risk and incidence of infection and corneal scarring in these susceptible patients, would represent a significant clinical and pharmacoeconomic advance in the treatment of this condition.

Detailed description:
In individuals with certain clinical conditions, such as diabetes, corneal epithelial defects persist and do not necessarily respond to conventional treatment regimens because of delayed epithelial wound healing. While wound closure should occur following an injury to the corneal epithelium, a timely re-establishment of the epithelial barrier is of utmost importance.

The wound repair process is intricately linked to a complex inflammatory response that must be properly regulated to ensure healing and optimal visual outcome. Infiltration of inflammatory cells into injured corneal tissue is a hallmark of wound repair, and the association of polymorphonuclear (PMN) leukocyte infiltration with sterile corneal ulceration is well recognized. Retardation of epithelial recovery by persistent inflammation, release of enzymatic products from degranulating PMN, and stimulation of mononuclear leukocytes by cytokines all contribute to poor re-epithelialization.

It has been shown that diabetic corneas manifest reduced rates of epithelial healing after denudement. Yet, in the diabetic patient, not only is the rate of corneal epithelial healing of clinical concern, abnormalities inherent in the diabetic corneal epithelial cytoarchitecture can cause substantial impediments to normal stromal healing. Histologically, diabetic corneas typically demonstrate thickening of the epithelial basal membrane (BM), decreased number of hemidesmosomes, and decreased number of nerve fiber endings. Studies of BM changes in diabetic corneas have yielded information regarding poor adhesion of the epithelial BM to the stroma. During vitrectomy in diabetic patients, when the cornea epithelium is removed, it separates as an intact sheet and the entire thickened BM, characteristic of diabetes, adheres to the epithelium. In contrast, when normal epithelium is removed by scraping, the BM remains adherent to the stroma.

Because patients with diabetic retinopathy (DR) corneas have delayed wound healing, the expression of thymosin beta 4 (Tβ4) as a potent epithelial cell migration stimulator in DR corneas was investigated. Human DR corneas were analyzed and were found to express significantly less Tβ4 compared to normal corneas, suggesting that the use of Tβ4 may accelerate the wound-healing process in this model.

Arms: arm 1: There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of eyedrops to the affected eye, identical to the active drug but with no thymosin beta 4 (0.00% thymosin beta 4, w/w), 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy). arm 2: There are 2 groups: active drug and placebo. The patients in the active comparator arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times a day (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).
Interventions: intervention 1: Thymosin Beta 4 (Tβ4) intervention 2: Placebo
Intervention descriptions: intervention 1: There are 2 groups: active drug and placebo. The patients in the active arm receive an administration of 0.01% Tβ4 (w/w) eyedrops to the affected eye, 2 drops 4 times daily (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy). intervention 2: There are 2 groups: active drug and placebo. The patients in the placebo arm receive an administration of 0.00% Tβ4(w/w) eyedrops to the affected eye, 2 drops four times a day (QID) (breakfast, lunch, dinner, and bedtime) for 14 days. The first of 4 daily doses will be administered following surgery (vitrectomy).

Protocol documents: