Losartan and tVNS for Post-Traumatic Stress Disorder

(ANG-P Trial)

This trial aims to understand why individuals with PTSD (post-traumatic stress disorder) often face a higher risk of heart disease and high blood pressure. It also examines why these individuals experience elevated adrenaline levels during stress. The study will test whether losartan, a medication, can lower these adrenaline levels and explore if a specific gene is linked to this issue. Participants will receive either losartan, atenolol (another medication), or undergo vagal nerve stimulation (a technique that may help relax the body) to determine which is most effective. Veterans with PTSD, who are not using certain heart or blood pressure medications and do not have conditions like diabetes or heart disease, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

You cannot participate if you are currently taking clonidine, beta blockers, ACE inhibitors, ARBs, or have used MAO inhibitors in the last 14 days. If you are on these medications, you would need to stop them to join the trial.

Previous studies have shown that losartan is generally safe and well-tolerated. The FDA has already approved losartan for treating high blood pressure, which supports its safety profile. In studies where losartan was used for PTSD, no major side effects were reported.

Research on transcutaneous vagal nerve stimulation (tVNS) also suggests that this treatment is safe. Studies indicate that tVNS is practical and does not cause major side effects. It has been used safely to treat stress-related disorders, including PTSD.

Researchers are excited about the treatments in this trial because they explore unique ways to address PTSD symptoms and related cardiovascular issues. Losartan, typically used for blood pressure management, is being investigated for its potential to reduce PTSD symptoms by blocking the effects of angiotensin II, a hormone that may contribute to stress responses. Atenolol, a beta-blocker, serves as a comparator to see if its heart rate-lowering effects can also impact PTSD symptoms. Additionally, transcutaneous vagal nerve stimulation (tVNS) offers a non-drug approach, potentially calming the nervous system by stimulating the vagus nerve. Unlike standard PTSD treatments that usually involve psychotherapy or medications like SSRIs, these options could offer new pathways to manage both mental and cardiovascular health in affected individuals.

This trial will evaluate the effectiveness of different treatments for PTSD. Participants will be randomized to receive losartan, atenolol, transcutaneous vagal nerve stimulation (tVNS), or sham tVNS. Studies have shown that losartan, typically used for high blood pressure, might help with PTSD by lowering adrenaline levels during stress. Some research suggests it could improve fear memory in mice, but human studies have not consistently shown a significant reduction in PTSD symptoms. Conversely, tVNS has shown promise in reducing PTSD symptoms by calming the body's stress response. It stimulates a nerve in the neck, which can help reduce anxiety and improve mood. While both treatments show potential, more research is needed to fully understand their effectiveness in treating PTSD.²⁶⁷⁸⁹