Clinical Trials and Treatments for IIH

The North American Neuro-Ophthalmology (or NANOS) organization hosts a meeting every year for neuro-ophthalmologist to showcase care updates, advances in research, and more. This year NANOS celebrated their 50^th anniversary and had a humongous turn out of physicians, students, and researchers alike!

As a PhD candidate focusing on idiopathic intracranial hypertension (IIH), I attended as typically a heavy portion of the NANOS meeting focuses on IIH. This year did not disappoint with many discussions on clinical trials, potential new therapies, recommended treatments, and discussions regarding fulminant IIH. Because so much was discussed during this meeting, I have decided to post two different posts to cover it. Today’s will focus on clinical trials involving IIH and my future update will be regarding other IIH updates including fulminant IIH.

What is a clinical trial? Why are they important? What is randomization? Why aren’t there more in IIH?

What is the IIHT?

First, let’s discuss what is a clinical trial and why are they important? Clinical trials are scientific experiments designed to evaluate the benefits of new therapies and treatments compared to prior treatments for patients with a certain condition. These are highly regulated trials that must undergo strict ethical review. Typically, these trials are conducted under randomization, which means that patients are randomly assigned to either the old treatment or new experimental treatment. In many cases, the entire research team is also blinded as to which treatment the patient is getting. These types of studies are extremely valuable because of these random assignments which remove lots of potential biases that can occur in studies.

The problem with clinical trials is that they are expensive and very hard to conduct! This requires a lot of time commitments from the patients involved and the research team. Also, for a disease like IIH which is relatively uncommon, it is extremely hard to find enough patients to enroll in these studies! This is why there are only 6 published clinical trials to date. Mollan et al. published an excellent summary of these clinical trials and other retrospective studies which I am referencing here¹. I have also included the summary images from this paper below.

(These images were taken from the published Cephalalgia article¹)

Probably the most famous IIH clinical trial is what we call the IIH Treatment Trial conducted by Dr. Michael Wall in 2014. This trial showed the effectiveness of acetazolamide (also called Diamox) in improving visual outcomes with patients with mild vision impairment².

Many of us were excited with the idea of a new clinical trial (IIH EVOLVE) looking at GLP1 drugs for IIH treatment, unfortunately this trial was closed with one of the reasons being struggling to find eligible patients to participate in the study. This continues to show just how hard it is to conduct trials for IIH! NANOS discussed the challenges of having IIH clinical trials extensively, but also their hope to conduct successful trials in the future!

Hope is not lost and research regarding treatments for IIH continues. Research regarding GLP1 receptor agonists has also continued. Dr. Olivia Grech, a scientist in Birmingham, UK presented her research on GLP1 at the NANOS meeting. Dr. Grech works at one of the premier IIH research groups in the world! This group is led by Dr. Susan Mollan (https://research.birmingham.ac.uk/en/persons/susan-mollan)  and Dr. Alexandra Sinclair (https://www.birmingham.ac.uk/staff/profiles/metabolism-systems/sinclair-alexandra). Dr. Grech used animal models in her work with GLP1 receptor agonists and showcased how these medications seem to reduce pain responses while helping to lower intracranial pressure. Hopefully this exciting finding will soon be tested in other ways and further improve our knowledge on how GLP1’s may help IIH patients.

In addition to GLP1’s, there was lots of discussions on different surgery techniques in relation to IIH outcomes. Typical surgeries for IIH include: ventriculoperitoneal shunting and lumboperitoneal shunting, optic nerve sheath fenestrations, and dural venous sinsus stenting. It is important to note there are no randomized control trials evaluating and comparing surgical IIH treatments to each other. This has probed a call in the IIH community highlighting the need for more research evaluating surgical outcomes^3–5. Dural venous sinus stenting is the newest surgical method for treating IIH and involves opening up drainage veins in the skull that have been compressed by an unknown cause. Several groups at NANOS reported data regarding patient improvements with this method, which is assisting science. The more research available, the better we can identify improved therapies for patients. However, clinical trials are still needed to prove effectiveness of this surgical method.

Image Source⁶

Overall, lots is in the works regarding treatments for IIH. There are multiple groups working to better understand surgical methods and outcomes in IIH. This could revolutionize IIH care and provide patients with faster more efficient treatments. Work is also still being done to better understand GLP1’s and if they could serve as a viable treatment for IIH.

Thank you so much for reading this first newsletter with USA IIH! We look forward to posting a second newsletter summarizing other elements of IIH care. 

Scientific Publication References

1. Mollan SP, Fraser CL, Digre KB, et al. Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension. https://doi.org/101177/03331024231197118. 2023;43(8). doi:10.1177/03331024231197118
2. Michael Wall; Gideon Zamba; NORDIC Idiopathic Intracranial Hypertension Study Group. Pointwise Visual Field Change in the Idiopathic Intracranial Hypertension Treatment Trial | IOVS | ARVO Journals. Invest Ophthalmol Vis Sci. 2015;56(7):2234. Accessed July 6, 2022. https://iovs.arvojournals.org/article.aspx?articleid=2331995
3. Derdeyn CP, Wall M. Counterpoint: stenting for idiopathic intracranial hypertension should be trialed. J Neurointerv Surg. Published online June 21, 2023:jnis-2023-020404. doi:10.1136/JNIS-2023-020404
4. Piper RJ, Kalyvas A V., Young AMH, Hughes MA, Jamjoom AAB, Fouyas IP. Interventions for idiopathic intracranial hypertension. Cochrane Database Syst Rev. 2015;2015(8). doi:10.1002/14651858.CD003434.PUB3
5. Mollan SP, Grech O, Alimajstorovic Z, Wakerley BR, Sinclair AJ. New horizons for idiopathic intracranial hypertension: Advances and challenges. Br Med Bull. 2020;136(1):118-126. doi:10.1093/bmb/ldaa034
6. Reid K, Winters HS, Ang T, Parker GD, Halmagyi GM. Transverse Sinus Stenting Reverses Medically Refractory Idiopathic Intracranial Hypertension. Front Ophthalmol. 2022;2:885583. doi:10.3389/FOPHT.2022.885583/BIBTEX