narcolepsy – Little Did She Know

…Nearing the Starting Line for ALKS 2680 Vibrance-3

Editor’s Note: Since November, I’ve been working on approval to participate in the ALKS 2680 Vibrance-3 clinical trial for Idiopathic Hypersomnia patients. IH is a rare, neurological sleep disorder similar to narcolepsy that is just now getting the attention it deserves. If you have IH or you have a loved one with IH, feel free to follow along here and on my Facebook page, Little Did She Know. To learn more about the clinical trial, visit ClinicalTrials.gov.

It is just after 1 AM on December 31st. If all goes well, in just under seven and a half hours, I’ll receive my first dose for the ALKS 2680 Vibrance-3 clinical trial for #IdiopathicHypersomnia (IH). I’m not nervous about side effects or scared it won’t work. It’s an odd peace, a calm that can only come from Jesus. I know God has me on this path for a purpose. Whether the drug helps, hurts or ends up ineffective like all the others I’ve tried, I’ve given it all over to God. I’m just going through the motions so He can do His work.

Then why am I up at 1 AM, writing about this, you ask? I’m not sure. Could be excitement. Could be the Twix I had before bed. Could be my secondary #DelayedSleepTendency sleep disorder. That’s right, your girl here has not one but two sleep disorders that feud like the Hatfields and the McCoys.

If you read my last post, “…What the ALKS 2680 Vibrance-3 Clinical Trial for IH Is,” you know it’s been a bit of a journey to get to this point in the study. I’ve made three trips to Cleveland Clinic specifically for this clinical trial so far: the initial physical exam/testing appointment, the eye exam required for the study and now a three-day sleep study appointment. I’ve also had to wear an actigraphy watch for the last 10 days, and I started my 14-day Adderall washout 18 days ago. So, let’s talk about this three-day visit and nearing the finish line on meeting the participation requirements.

L-R: On a flight to Akron after the Cleveland flight was cancelled, and arriving at the Cleveland Clinic main campus after a rocky start. Can you tell I was so tired that morning, I forgot to brush my hair?

I arrived in Cleveland on Monday, December 29. Getting here in itself was a side quest. I had to fly from Charleston, WV, to Charlotte to Cleveland – yes, I had to go south to go north – and upon arriving in Charlotte for my connection, the Cleveland flights were cancelled due to wind from the winter storm in the Great Lakes region. I was rerouted to Akron, Ohio, and then took a 48-minute Lyft ride with a lovely driver named Janelle. Considering I had been off my stimulant for 16 days at that point and had not had any caffeine in two days as a requirement of the sleep studies, I think I navigated that situation pretty well.

When I arrived on Monday, I did some additional questionnaires and last-minute prep work for the sleep studies in the clinical trial wing at the Cleveland Clinic. Then I checked into my hotel and took a nap before returning to the hospital for the scheduled polysomnography (PSG) and the maintenance of wakefulness test (MWT).

I mentioned in “…What the ALKS 2680 Vibrance-3 Clinical Trial for IH Is” that the PSG is the nighttime test given to diagnose sleep apnea, and it’s the first of two sleep studies used to diagnose narcolepsy and IH. If a patient passes the PSG, they stay in the clinic to continue an MSLT for Narcolepsy or IH diagnosis. This was my third PSG, and I passed it with flying colors.

In my last post, I explained that diagnosis also requires the multiple sleep latency test (MSLT), which is a series of nap opportunities spaced two hours apart over 8 to 10 hours during which the patient is in bed in a dark room and is told to try to go to sleep. During an MSLT, the following is measured: if the patient goes to sleep, how fast the patient goes to sleep, if the patient hits REM and how fast the patient hits REM. Each opportunity is 30 minutes, and if the patient falls asleep, they are allowed to sleep up to the 30-minute window.

Similarly, the MWT places the patient in a darkened room, sitting up in bed instead of lying down. Like the MSLT, this test is done every two hours over an 8 to 10 hour period. The test measures if the patient falls asleep and how quickly they fall asleep. As soon as the patient falls asleep, the test facilitator wakes them up. For both tests, the patient must stay awake for the time between each nap opportunity.

L-R: (Left) Tuesday morning, we removed all the wiring except the electrodes that measured brain activity necessary for the MWT. (Middle) After MWT nap #1; I don’t know if you can see how tired I was, but I fell asleep twice playing one of the brain games. I’ve never done that before. (Right) Dressed and ready to go back to the hotel after a grueling 24 hours of sleep tests.

During the MWT, they also had me doing tests – or brain games – on an iPad to check my memory skills and my response time while being without stimulants or naps. They will use the PSG and MWT results to confirm my diagnosis, get approval for my receiving the medication and document a baseline, and they will use the computer games throughout the clinical trial to look for any improvements while on the new drug as compared to the results taken during the MWT.

Later this morning, I’ll return to the clinic to find out if I’m approved to receive the medication in the blind study. We expect a yes, especially since I fell asleep within 5 to 10 minutes of lights out yesterday for three of the four naps (we had some outside stimulant interference that had an impact on the last nap). If we get the go, I’ll have another physical exam by a doctor this morning and complete more blood work and an EKG. I’ll then receive my first dose at 8:30 AM, and they will monitor me for a while after taking that dose because initial side effects with the first dose varied among narcolepsy patients, and I’ll be the first IH patient at Cleveland Clinic to receive the medication.

If approved to begin, I’ll report back to Cleveland Clinic every two weeks for an in-person check-up, additional testing like another eye exam and blood work and to receive the next two weeks’ worth of medication. The trial is a blind study, so no one knows if I will get an actual dosage of the medicine or a placebo. In about 8 weeks, I’ll have to come back and do another sleep study test series to compare results.

When I agreed to this trial, I knew there would be a lot of visits to Cleveland. I didn’t remember what it felt like to not be on Adderall, and while I knew coming off of it in the washout would be hard, I underestimated how hard that would be. I’ve been a complete zombie since I came off the Adderall, napping two and three times a day, and it’s still not enough. The sleep inertia is terrible, my productivity for everything is low, and I am irritable. But I trust God to see me through this.

Because here’s the thing. After God moved mountains for me in hurricane season, I know without a doubt He’s got my back. He’s already at the end of this study. He’s already fought the battle for me. Whatever happens – whether this drug helps or doesn’t – He’s already got it all worked out. I feel like He’s leading me into this study, and something really special is going to come out of it. (Read about God moving mountains in hurricane season here: “…She’d See God Move Mountains.”)

Trust me, kid. I’ve got you.

I don’t like flying, and the flight into Akron was particularly rocky. To distract myself, I stuck an earbud in my ear and turned on my “God” playlist on my phone. I heard a really cool song by Anne Wilson that I had never listened to before, and I want to share it with you. The song is called “Scatter,” and the lyrics say:

“Before I hit the front line, You’ve already gone before. I know that I know the battle is the Lord’s.”

…What the ALKS 2680 Vibrance-3 Clinical Trial for IH Is

Blogger’s Note: About a month ago, I shared some information on my #chronicillness, #IdiopathicHypersomnia (IH). As I get closer to the start date for the clinical trial, I wanted to share some background information for those who have Narcolepsy or IH or those who have a loved one with one of these neurological sleep disorders that might find info about the clinical trial helpful.

I have pulled the following information specifically from a press release published by Alkermes (www.alkermes.com, a neuroscience-based research organization that “develops medicines designed to help people living with complex and difficult-to-treat psychiatric and neurological disorders”). You can find the press release about ALKS 2680 Vibrance-3 here.

Before I share with you the crazy process of being approved as a participant in a clinical drug trial, let’s talk about what the ALKS 2680 Vibrance-3 trial is. Because when I tell you all the things I’ve had to do – and am still doing – to be approved for the trial, you may question whether it’s worth it.

What is Idiopathic Hypersomnia?

“Idiopathic hypersomnia (IH) is a rare, chronic, neurological sleep disorder characterized by excessive daytime sleepiness despite normal sleep durations. Additional common symptoms can include severe sleep inertia (individuals may feel groggy or disoriented for prolonged periods after waking up), unrefreshing naps, fatigue and cognitive dysfunction. The underlying neuropathology of idiopathic hypersomnia is unknown. IH affects an estimated 40,000 people in America.”

What is the ALKS 2680 Vibrance-3 clinical trial?

According to the Alkermes press release published April 1, 2025: “…Alkermes plc (Nasdaq: ALKS) today announced the initiation of Vibrance-3, a phase 2 clinical study evaluating the safety and efficacy of ALKS 2680 compared to placebo in adults with idiopathic hypersomnia (IH). ALKS 2680 is the company’s novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development as a once-daily treatment for narcolepsy type 1, narcolepsy type 2 and IH – chronic, neurological disorders characterized by excessive daytime sleepiness.”

What is Orexin?

“Orexin, a neuropeptide produced in the lateral hypothalamus, is considered to be the master regulator of wakefulness due to its activation of multiple, downstream wake-promoting pathways that project widely throughout the brain. Targeting the orexin system may address excessive daytime sleepiness across hypersomnolence disorders, whether or not deficient orexin signaling is the underlying cause of disease.”

This part about orexin is really interesting to me. The way it was explained to me is that orexin is a chemical in the brain that promotes wakefulness. In Narcoleptics, the orexin pathway is destroyed, preventing the orexin from supporting wakefulness. In IH patients, the pathway is disrupted (but not destroyed!). The hope is Vibrance-3 will address the pathway issues to deliver the orexin and lead to more wakefulness in Narcolepsy and IH.

How does this trial work?

“Vibrance-3 is a phase 2, randomized, double-blind, dose-range-finding, placebo-controlled study evaluating the safety and efficacy of ALKS 2680 in adults with IH.” Basically, I will randomly get a dose of ALKS 2680 (10mg, 14 mg or 18mg) or receive the placebo every two weeks for eight weeks. No one knows what dosage I will get each time. “The primary endpoint will assess, by dose level, whether participants taking ALKS 2680 experience a greater decrease in sleepiness compared to participants taking placebo alone, as measured by the change in Epworth Sleepiness Scale (ESS) score.”

How many participants are participating?

This study is expected to have 96 IH patients from the U.S., Australia and Europe. Last I heard, there are eight countries participating. I have accepted one of five slots available at the Cleveland Clinic. I know Cleveland is looking for more participants, so if you have IH and Cleveland is accessible, you should reach out to the Cleveland Clinic Sleep Disorder Center.

Why does this trial matter?

“The initiation of Vibrance-3 represents an important step forward for the ALKS 2680 development program as we seek to advance a potential new treatment option for people living with idiopathic hypersomnia. There remains high unmet need for the idiopathic hypersomnia community, as evidenced by a recent survey conducted by the Sleep Consortium in which more than 90% of patients surveyed indicated that IH symptoms had a moderate to high impact on their life,” said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President, Research & Development at Alkermes.

And it matters to yours truly because Adderall is the only other medication that has helped, despite the side effects, and it doesn’t help consistently. I have also tried Modafinil, Armodafinil, Sunosi, Jornay PM, Ritalin and Xywav, with no success or very little success combined with strong side effects.

Stick with me on this journey. Next up, I repeat sleep studies at the end of the month with the intention of starting Vibrance-3 – or a placebo – on New Year’s Eve.

…She Has Idiopathic Hypersomnia

Blogger’s Note: Follow my journey as I join an Idiopathic Hypersomnia clinical trial through Cleveland Clinic! If you have IH, know someone who has IH or just want to learn more about this rare sleep disorder, click follow at the bottom or check out Little Did She Know on Facebook.

All my life, I have struggled with sleep. I have always had a hard time waking up in the morning, and most of my life, I could sleep the day away if allowed. A typical nap has always been two or three hours if uninterrupted and still left me exhausted. Sleep has never been refreshing.

To look at me, I don’t necessarily think you would know there is a problem.

But there is a problem: idiopathic hypersomnia.

For starters, I have always struggled with being on time, especially in the morning. Now I know it’s due to sleep inertia. Sitting in meetings, classes and presentations at conferences always led to a struggle to stay awake regardless of what time of day it was. It did not matter how much sleep I got at night. I was still exhausted every day.

Sleep inertia or sleep drunkenness is defined by:

Difficulty waking up
Struggling to wake up fully (often with an overwhelming desire to go back to sleep)
Feeling disoriented, confused or irritable
Having poor coordination
Doing tasks without realizing it
May last for a few hours after waking up
www.hypersomniafoundation.org

I thought I was lazy because while there were things around me that needed to be done, I would find myself lying down to take a nap. I’m a driven person, so I didn’t understand how I could be lazy, and yet, there I was, taking a nap in the middle of the afternoon on a regular basis.

Idiopathic Hypersomnia, or IH, is a rare sleep disorder characterized by excessive daytime sleepiness (EDS) (a strong daytime sleepiness or need to sleep during the day, even with enough sleep the night before), sleep inertia, long sleep (needing at least 11 hours of sleep per 24-hour period or more than 9 hours at night), needed naps (may be hard or impossible to avoid; usually last more than one hour; are unrestorative; may make the patient feel even worse) and poor quality sleep at night.

Source: Hypersomnia Foundation

IH is a neurological disorder similar to Narcolepsy (minus the cataplexy and sleep attacks). “Idiopathic” means unknown cause, which means I don’t have another health issue that is causing the disorder. Since there is no cause, there is no cure. There are treatments to minimize symptoms, but only one treatment has had any impact on me, and it is unreliable relief because I never know when the medication is going to work well, work a little or not work at all. And then there are the side effects to deal with.

In addition to the excessive sleepiness, IH also causes a feeling similar to depression. It feels like I’m wearing a weighted blanket that’s trying to hold me down, even though I have my depression and anxiety controlled (confirmed by my therapist and psychiatrist).

In fact, it can be confused with depression, and I think that’s part of why diagnosis is so hard to come by. It can take an average of 10-15 years to get a diagnosis of IH. My earliest memory of seeing a doctor about my “fatigue” was at the age of 21 being checked for chronic fatigue and testing to see if I had had mono at some point. I’ve been actively complaining about sleepiness since then.

IH causes brain fog. I have to work harder to focus and get things done both with my job in disaster at the American Red Cross and in my personal life. Have you heard of the “spoon theory?” It’s a metaphor for explaining the energy limitations of people with chronic illness. Each day, I have to pick the most important things I’m going to get done.

This Spoon Theory image and additional information can be found at https://kaleidoscopefightinglupus.org/spoon-theory/.

The similarities between IH and narcolepsy types 1 and 2, according to the Hypersomnia Foundation, are excessive daytime sleepiness and brain fog. IH and narcolepsy type 2 are more likely to have in common long sleep and severe sleep inertia. One difference, however, is that IH causes the need for long naps that are unrefreshing – like, you can’t fight the nap, but when you wake up, you’re no better off.

Comparison chart and additional information can be found at https://www.hypersomniafoundation.org/classification/.

Diagnosis of IH is a long process – clearly, 15-years long for some. For me it was at least 22 years. First, you need to find a good doctor who is knowledgeable about and experienced with IH. Then, your doctor will eliminate all of the normal causes for fatigue, like B12 deficiency and thyroid issues. Next, your doctor will order sleep studies.

The sleep studies consist of two parts in a 24-hour period: the PSG and the MSLT. The polysomnography (PSG) is an overnight test used to diagnose sleep apnea by monitoring you while you sleep. If the test determines you have sleep apnea, you don’t do the second part of the test. The doctor will address the sleep apnea first to see if that resolves the issues you’re having.

If you pass the PSG, you stay at the testing site to do a Multiple Sleep Latency Test (MSLT) where you are closely monitored and instructed to try to take a nap once every two hours to see if you fall asleep, how quickly you fall asleep and if you hit REM. After 30 minutes the test stops, and an hour and a half later, you go again. This is repeated four to five times in the same day. If you have excessive daytime sleepiness, this is brutal.

I am on my third IH doctor. By the time I got my diagnosis, I was no longer willing to put up with doctors who were unwilling or unable to help me. Now, my IH is managed by Dr. Foldvary, the director of the Cleveland Clinic Sleep Disorder Center. She is amazing. She thinks outside the box, and she never gives up. She is the one who got me into a new clinical trial.

Clinical trial physical and prep work, followed by a pre-trial eye exam at the Cleveland Clinic Cole Eye Institute.

Fingers crossed we’re on to something with the clinical trial. If not, I’ll keep on keeping on because I’ve got stuff to do – like fostering kittens and going to Hogwarts and doing volunteer work – regardless of how many spoons I have or if I need a nap in the middle.