Medscape – BOSTON — Results of a small study of an intranasal version of the hormone oxytocin indicate that the agent may be helpful in the management of chronic migraine. The single-dose, placebo-controlled, double-blind study found the agent, currently called TI-001, to be safe and highly effective.
The study, which was presented here at the 2013 International Headache Congress (IHC), included 40 patients with chronic migraine who received a dose of the agent and were asked to rate their pain, nausea, photophobia, and phonophobia on a 4-point scale (indicating severe, moderate, mild, or none) prior to and at 0.5, 1, 2, 4, and 24 hours.
At from 2 to 4 hours, 64% of the patients who received the agent reported a reduction in pain by 2 categories (either from “severe to mild or none,” or from “moderate to none”) compared with only 27% of patients who received a placebo.
“You start to see a separation of oxytocin and placebo at about 2 hours, and then at 4 hours, it’s a bigger effect; at 24 hours, you still see some improvement,” said David C. Yeomans, PhD, director of pain research at Stanford University School of Medicine in California and chief scientist and founder of Trigemina, Inc., the company developing the product.
The body produces oxytocin to induce labor and promote lactation, but its strongest release comes during sexual orgasm in both women and men. The current liquid intranasal formulation of the hormone is inhaled up one nostril to reach and cover the nasal mucosa, said Dr. Yeomans.
This intranasal method of delivery bypasses the blood-brain barrier and directly accesses the part of the nervous system that is involved in chronic migraine, he said. The idea, said Dr. Yeomans, is to concentrate the hormone in this trigeminal system to access oxytocin receptors and decrease pain-evoked neural activity and therefore head pain.
Experiments in rats have demonstrated this scientific phenomenon: after application of oxytocin, the hormone is preferentially taken up throughout the trigeminal system. “It goes directly to the trigeminal nerve, which provides all the pain information from the head,” explained Dr. Yeomans. “If you put oxytocin in the nose of rat, you see high concentrations all through the trigeminal system, so it’s really concentrating there.”
The researchers noted that those patients who had taken a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen prior to treatment did much worse than those who did not take such a drug. None of the patients who took an NSAID responded at the half-hour or 1-hour time points, and many fewer responded the rest of time compared with those not taking an NSAID.
Dr. Yeomans explained that inflammation causes a 5-fold increase in oxytocin receptors in the trigeminal system, “so there’s a whole lot more for oxytocin to target,” but an NSAID will block this inflammation.
The study also found that compared with placebo, the nasal oxytocin decreased the percentage of patients with nausea, photophobia, and phonophobia.
The company is now carrying out a phase 2b study of efficacy, tolerability, and safety involving about 100 patients with chronic migraine, said Dr. Yeomans. “We hope to start that phase 3 study probably in about a year from now, and it will probably take one and a half years to complete, so the product might be available within about 3 years,” he added.
Oxytocin is also being investigated as a treatment for autism.
The study was funded by Trigemina, Inc. Dr. Yeomans is chief scientist and founder of Trigemina, the company developing the intranasal product.
2013 International Headache Congress. Abstract P59.
July 3, 2013