Curcumin clinical trials

James, J.S., Curcumin clinical trial finds no antiviral effect, AZD5 Treat. News, (242), 1-2, 1996. 

Sharma, R.A. et al.. Phase 1 clinical trial of oral curcumin biomarkers of systemic activity and compliance, Clin. Cancer Res., 10, 6847, 2004. 

Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. (2008) Curcumin From ancient medicine to current clinical trials. Cell Mol Life Sci 65 1631-1652. 

Curcumin represents a covalent inhibitor of CBP. Beyond, it showed anti-angiogenic effects and is currently in phase II/III of clinical trials for cancer therapy, as well as in phase II for Alzheimer s disease and psoriasis [21, 22[. Garcinol, a potent inhibitor of PCAF and p300 (IC50 = 5 and 7 J-M, respectively) was found to induce apoptosis and alter global gene expression in HeLa cells. It was identified to repress chromatin transcription. N one of these inhibitors had effects on H D AC activity or on histone-free DNA transcription [23]. 

Studies during the past century have shown the anticancer effect of curcumin against cancers of various anatomical sites. The preclinical anticancer potential of curcumin has been established both in vitro and in vivo, which lead to the clinical trials with this promising molecule. Below is a description of the studies, that have evaluated the preclinical and clinical anticancer activity of curcumin. 

Several clinical trails are reported with curcumin in cancer patients around the world. Some of our recent review [Anand et al., 2008 Goel et al., 2007 Kunnumakkara et al., 2008] gives a detailed description of the clinical trials with curcumin, which are summarized in Table 16.2. An early clinical trial evaluated the effectiveness of topical application of a curcumin ointment in patients with external cancerous lesions. Patients with cancers of oral cavity (37 patients), breast (7 patients), vulva (4 patients), skin (3 patients), and miscellaneous unspecified sites (11 patients) were enrolled in this study. Remarkable symptomatic relief was observed in this study with the reduction in smell in 90% of the cases, reduction in itching in almost all cases, and reduction in exudates in 70% of cases. Reduction in lesion size and pain was observed in about 10% of the cases and only one melanoma (scalp) patient showed an adverse effect of local itching, which may be due to the allergic reaction to curcumin. 

Table 16.2 A List of Clinical Trials with Curcumin in Cancer Patients 2...

In another clinical trial, researchers evaluated the effect of oral curcumin with piperine on the pain, and the markers of oxidative stress in patients with tropical pancreatitis (TP). Twenty patients with tropical pancreatitis were randomized to receive 500 mg of curcumin with 5 mg of piperine, or placebo, for 6 weeks, and the effects on the pattern of pain, and on red blood cell levels of malonyldialdehyde (MDA) and glutathione (GSH) were assessed. There was a significant reduction in the erythrocyte MDA levels following curcumin therapy compared with placebo with a significant increase in GSH levels. There was no corresponding improvement in pain. 

Tunstall RG, Sharma RA, Perkins S, Sale S, Singh R, Farmer PB, Steward WP, Gescher AJ. 2006. Cyclooxygenase-2 expression and oxidative DNA adducts in murine intestinal adenomas Modification by dietary curcumin and implications for clinical trials. Eur J Cancer 42 415-421. 

Strimpakos AS, Sharma RA. 2008. Curcumin Preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10 511-545. 

James led a New England clinical trial of curcumin s effectiveness as an antiviral agent in 40 participants. Two dropped out 23 were randomized to a high-dose group (four capsules, four times a day) and 15 to a low-dose group (three capsules, three times a day) for 8 weeks. Though it had no antiviral effects, curcumin was well tolerated, and most participants liked taking curcumin and felt better. 

Botanical agents that have been shown to inhibit Cox-2 activity in vitro include holy basil,3 curcumin, ginger and related products," -" green tea, hops, ber-berine, and willow bark." However, in spite of extensive laboratory evidraice that these botanical agents can inhibit Cox-2 in vitro, and promising results from clinical trials (e.g., of ginger and willow for pain" ), it has not yet been demonstrated that oral consumption of botanical agents can inhibit Cox-2 activity in humans. 

A review of clinical trials of turmeric and the compound curcumin indicated that turmeric and curcumin were generally safe and well tolerated at doses up to 8 g daily for 4 months. Adverse events reported in human pharmacological studies (see below) were primarily diarrhea or nausea, with other events reported as headache, rash and yellowish stool (Hsu and Cheng 2007). 

Cheng, A.L., C.H. Hsu, J.K. Lin, et al. 2001. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 21(4B) 2895-2900. 

NCT01294072 Phase I clinical trial investigating the ability of plant exosomes to deliver curcumin to normal and malignant colon tissue... 

On a note of caution, however, there is still insufficient data to support the clinical use of flavonoids in the treatment of neurodegeneration, and there have been a number of disappointing results from human intervention studies for dementia with various dietary polyphenolics and antioxidants such as curcumin and Gingko bUoba. The challenge ahead, therefore, is to proceed cautiously until rigorous randomized controlled clinical trials have been undertaken to determine empirically if flavonoids have efficacy in individuals affected by dementia and other neurodegenerative conditions. 

---