A cheap, over-the-counter oral supplement made standard treatments for vaso-occlusive crises in sickle cell disease more effective, a researcher said here, with substantial implications for the disease in Africa as well as in more developed parts of the world.
Among 68 Nigerian children with sickle cell anemia in vaso-occlusive crisis randomized to placebo or 100 mg/kg oral L-arginine three times daily for 5 days in addition to normal analgesic medication, the agent was associated with significant reductions in pain scores beginning on the second day of treatment relative to placebo, reported Richard Onalo, FCPaed, of the University of Abuja in Nigeria.
On the standard 10-point scale of self-reported pain severity at baseline, children in the L-arginine and placebo groups scored 8.7 and 8.4 on average, respectively, he reported at the American Society of Hematology (ASH) annual meeting. Scores in both groups declined by day 2, but the gap between them grew to 2 full points, and by day 5, the L-arginine group still reported significantly less pain. At that point, mean scores stood at about 4.0 versus 2.8, with a P-value of 0.006 for the time trend.
Furthermore, total analgesic drug doses were cut 39% (P<0.001), and time to resolution of crisis (defined as pain score <4) was significantly shorter with the supplement: this endpoint was reached by nearly half of the L-arginine group by day 4, compared to less than 25% of those on placebo.
Hospital stays were shorter as well, with means of 110 versus 156 for L-arginine versus placebo. By day 5, 54% of L-arginine patients were discharged, versus 24% of the placebo group, Onalo said. Moreover, it was day 11 when the last L-arginine patient was discharged, compared to day 15 in the placebo group.
To dose the L-arginine, investigators mixed a 100-mg/mL liquid solution into grape juice for the children to drink.
There were no safety issues of any kind, and a larger phase III trial is warranted, Onalo said at an ASH press briefing on his results.
The rationale for L-arginine to treat vaso-occlusive crisis is that the amino acid is generally depleted in sickle cell disease. This deficiency worsens during these crises, which are marked by decreases in nitric oxide, the potent short-acting vasodilator that requires arginine for its generation. Thus, supplementing with arginine could increase nitric oxide availability to relieve the crises.
A number of previous studies have supported this hypothesis, most notably another small trial published in 2013 that also found a benefit for pain relief, hospital stay, and opioid use. Similar results were also seen in a Brazilian trial among adults published earlier this year.
Yet despite these and other publications suggesting a benefit from arginine, not to mention its wide availability and low cost, it has not gained traction either among physicians or the patient community, said ASH press briefing moderator Julie Panepinto, MD, of the Medical College of Wisconsin in Milwaukee. She told MedPage Today that no parent has asked her about it.
She noted that there have been some trials in the U.S. testing arginine for prevention with negative results, and it would be “too early” for patients or their parents to try it at home. Studies are in the works to examine the agent for relieving sickle cell pain and, importantly, to establish optimal dosing.
But with regard to Onalo’s study, “this is really exciting… to finally see some positive findings that should lead us to future work to really understand better how to use this medication.”
Ajinomoto supplied the L-arginine.
Onalo disclosed no relevant relationships with industry. One co-author disclosed intellectual property interests related to the work.
Primary Source
American Society of Hematology
