Garlic has been known to have antiplatelet properties. Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy. During this project we tested aged garlic extract (AGE), a commercial garlic preparation, with warfarin (Coumadin). Sixty-six (66) patients were screened for a double-blind, randomized, placebo-controlled pilot study. Fifty-two (52) patients were randomized for the project. Forty-eight patients (30 men and 18 women, with a mean age of 56+/-10 years) completed the study. Eighteen patients (14 before randomization, 4 after randomization) were dropped from the study. The study medication (AGE or placebo) was administered at a dose of 5 mL twice a day for 12 wk. Potential bleeding and thromboembolic episodes were monitored. There was no evidence of increased hemorrhage in either the placebo or the AGE group. Adverse events included headache, fatigue, colds, and dizziness. However, no significant difference was found in the incidence of these minor adverse events between the groups. Thus, the adverse events are unlikely to be attributable to AGE. The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy. Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary, its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications.
Background:There remains an unmet medical need for new treatments for patients with sickle cell disease (SCD). Increased oxidant stress plays a major part in the pathophysiology of sickle cell disease. It can lead to disturbance of cell membranes, exposure of adhesion molecules and damage to the contents of the sickle red blood cells (sRBC). Previous work from our laboratory has demonstrated enhancement of nicotinamide adenine dinucleotide (NAD) in sRBC by supplementation with a precursor of NAD, L-glutamine. A multi-center Phase 2 placebo-controlled trial in patients with SCD utilizing oral prescription grade L-glutamine resulted in a trend for a decrease in the incidence of painful crises at 24 weeks and a statistically significant decrease in hospitalization during the same time period in the L-glutamine group without increased adverse events. Based on these results, a large multicenter Phase 3 clinical trial was undertaken to evaluate the efficacy and safety of prescription grade L-glutamine therapy in patients with SCD. Methods: A randomized (2:1), double-blind, placebo-controlled, parallel-group trial was conducted at 31 sites across the United States. Subjects were stratified by hydroxyurea usage. Eligibility criteria included patients ≥ 5 years of age with documented diagnoses of HbSS or HbS/β0-thalassemia with at least two documented episodes of sickle cell crises (SCC) diagnosed in a medical facility during the 12 months prior to screening. Pregnant women and patients with uncontrolled liver disease or renal insufficiency were excluded. Prescription grade L-glutamine at 0.6 g/kg/day (max 30 g), or placebo, was taken in two divided doses. Daily dose was rounded to the closest 10 g. The study drug was given for 48 weeks, then was tapered to zero over 3 weeks and a final evaluation visit was made 2 weeks after last dose. The primary endpoint was number of SCC; secondary endpoints include rates of hospitalization and adverse events; additional analyses include cumulative hospital days, incidence of acute chest syndrome (ACS) and time to first crises. Results:A total of 230 patients were enrolled; ages 5-58; 53.9 % female. 152 were assigned to L-glutamine and 78 to placebo; the groups were well balanced for clinical characteristics. The median incidence of SCC was significantly lower in the treatment group compared to the placebo group (3 events vs. 4 respectively; p=0.008); The median incidence of hospitalization was significantly lower in the treatment group compared to placebo group (2 events vs. 3 events respectively; p=0.005); Median cumulative hospital days were significantly lower by 41% in the treatment group (6.5 days) compared to the placebo group (11 days) (p=0.022); 11.9 % of the L-glutamine group and 26.9% of the placebo group were affected by acute chest syndrome (ACS) (p=0.006). The median time to first crisis was 54 days in placebo group and 87 days in treatment group (p=0.010). Adverse events in the treatment arm were similar to those observed in the placebo arm. Statistically significant improvements for the frequency of painful crises and hospitalization persisted with analysis stratified by hydroxurea use, age, and gender. Conclusion: This Phase 3 study in SCD demonstrated that treatment with prescription grade L-glutamine provided clinical benefit over placebo by reducing the frequency of painful crises and hospitalization. Additional clinical benefit was observed when evaluating ACS, time to first crises and duration of hospital stay. There was no increase in adverse events compared to placebo. Prescription oral L-glutamine is easy to administer and does not require special monitoring. Disclosures Niihara: Emmaus Medical Inc: Employment, Equity Ownership. Tran:Emmaus Medical Inc: Employment, Equity Ownership. Razon:Emmaus Medical Inc: Employment. Macan:Emmaus Medical Inc: Employment. Stark:Emmaus Medical Inc: Employment, Equity Ownership. Wun:Emmaus Medical Inc: Consultancy; Pfizer: Steering Committee Other. Adams-Graves:Emmaus Medical Inc: Consultancy.
Background: Our earlier work suggested an enhancement of nicotinamide adenine dinucleotide (NAD) in sickled Red Blood Cells (sRBC) by administering a precursor of NAD, L-glutamine. We hypothesized that L-glutamine would decrease the incidence of painful sickle cell crises (PSCC). Small proof of concept studies led to the development of a multi-center Phase 2 placebo-controlled trial where oral pharmaceutical grade L-glutamine (PGLG) suggested benefit when measuring PSCC incidence at 24 weeks. A large multi-center Phase 3 trial further demonstrated that there was a reduction in the incidence of PSCC by administering PGLG compared to placebo. Additional analyses on the data from this trial were conducted and we are reporting our evaluation on the severity of crises between treatment arms. Methods: A randomized (2:1), double-blind, placebo-controlled, parallel-group Phase 3 study was conducted at 31 sites in the United States. Subjects were stratified by hydroxyurea usage. This study included subjects 5 years of age and older that had at least 2 PSCC during the year prior to enrollment. The primary endpoint for the Phase 3 trial was the number of PSCC between treatment arms. Since PSCC events were adjudicated by a blinded third party committee and data were collected as an adverse event ranked as "None"(0), "Mild" (1), "Moderate" (2) and "Severe" (3), the difference in "Severity" of PSCC between treatment arms using Cochran Mantel Haenszel (CMH) Ranked Scores statistics was evaluated post-hoc. Each patient was counted only once at the highest level of severity. Results; A total of 230 patients were enrolled; ages 5-58; 53.9 % female; 152 were assigned to PGLG and 78 to placebo; and the groups were well balanced for baseline clinical characteristics. The comparison of Severity for PGLG vs. Placebo indicated that at (0) was 24% vs. 10% respectively; at (1) was 6% vs. 8%; at (2) was 36% vs. 35%; and at (3) was 34% vs. 47%. Summary statistics for the cohort taken as a whole indicated a treatment difference benefit for the PGLG treatment (p = 0.0167). Other adverse events in the PGLG arm were similar to those observed in the placebo arm. Conclusion: PGLG therapy may be providing clinical benefit over placebo in adult and pediatric patients with a history of two or more crises per year by reducing the "Severity" of painful crises. Difference appeared to be driven by (0) or "None" PSCC events and by a decrease in (3) "Severe" PSCC events. PGLG was administered without difficulty and did not require special monitoring. Disclosures Niihara: Emmaus Medical, Inc: Employment, Equity Ownership. Tran:Emmaus Medical, Inc: Employment, Equity Ownership. Razon:Emmaus Medical, Inc: Employment. Stark:Emmaus Medical, Inc: Employment, Equity Ownership. Macan:Emmaus Medical, Inc: Employment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.