Restless Legs Syndrome Foundation Blog

Study: Hemoglobin Levels, Not Serum Ferritin, May Indicate a Better Response to Iron Intervention

Iron is fundamental to the healthy functioning of the body’s organs, including the brain. Its connection to the production of red blood cells is also a major determining factor in clinical practice when prescribing iron intervention. However, according to some scientists, the guidelines for iron replacement in neurological disorders, such as restless leg syndrome (RLS), are poorly defined.

“The current thinking, although not supported by all RLS physicians, is that serum ferritin levels are a measure of iron status and serve as a guidepost for iron replacement therapy," said RLS Foundation Scientific and Medical Advisory Board Member, Dr. James R. Connor. However, new research conducted by Connor and his team, and published in Fluids Barriers CNS, suggests that a patient’s hemoglobin levels may be a better indicator in determining the treatment guidelines for iron therapy.

The researchers conducted a preliminary research study to determine if the body’s iron status is communicated to the brain and they were able to show that iron transport does relate positively with hemoglobin (iron level measurement in the blood), but not with serum ferritin levels.

The team created a model to test their hypothesis. Using a cell culture model to mimic the blood vessels in the brain, they placed transferrin complexed with iron on one side of the cells (representing the blood side) and they put human cerebrospinal fluid on the other side of the cells which represented the brain side. The cerebrospinal fluid was randomly selected from more than 350 individuals enrolled in a study at Emory University for symptoms of excessive daytime sleepiness or other neurological disorders of excessive daytime sleepiness such as narcolepsy. Four additional samples came from an RLS study at Johns Hopkins University. Study samples were derived solely from females of northern European ancestry between the ages of 35 to 66 who were not considered anemic, a condition lacking healthy red blood cells.

The scientists said according to their findings, "the demand for iron for the production of blood cells in the bone marrow outweighs brain iron requirements. Thus, the study is showing that serum ferritin level, which is the traditional metric that is thought to reflect total body iron stores and relied upon to inform treatment decisions, may not be the preferred lab test when attempting to promote brain iron uptake.”

Connor said the data suggests that the hemoglobin levels may be a better indicator of which patients will respond to iron intervention and explains some of the individual differences in responders. "The data in this study supports physicians who consider serum ferritin levels an insufficient measure to determine which patients will respond to iron interventions. The next step would be to evaluate how hemoglobin levels impact response to iron treatment in RLS in a large population study."

About the Survey

Why should I take the RLS Patient Odyssey Survey II? – Data collected in the Patient Odyssey Survey II will offer researchers information on the long-term burden of disease, leading to improved medical treatments and improved quality of life. Your input matters! “This study will provide data to accelerate and focus our efforts to address these challenges and improve quality of life for RLS patients and their families.” -Karla Dzienkowski, Executive Director, RLS Foundation.

Who can take the survey? – The Patient Odyssey Survey II is open to anyone with RLS worldwide, with a separate survey open to partners or caregivers living in the same household.

Where can I find the survey links? – The patient and partner survey can be found on our website at: www.rls.org/odyssey. Or you can access the surveys directly on the survey platform website (see below).

How long will it take to complete? – The patient survey should take approximately 60 minutes to complete, and the partner/companion survey will take about 20 minutes to complete. However, you do NOT have to complete the survey in one sitting; the deadline to submit responses is Friday, October 23, at midnight.

Can I request a paper copy? – Absolutely! Contact us, and we can send you a printed survey with a return envelope. We can only mail to US addresses. Email maddie@rls.org to request a copy and be sure to include your name and mailing address. Be sure to mail your survey back to us by Friday, October 23.

How will the results be shared? – Results will be shared with the RLS community and the public in 2021, prepared for publication in the medical literature and presented in scientific meetings. Findings will also be shared with health policymakers through the RLS Foundation's Advocacy Initiative. It is important to note that protecting your privacy is of utmost importance to us.

Will my responses be confidential? – Your responses will remain confidential and anonymous. No individual identifying information is requested of or collected from survey participants.

Completing the Survey

What if I need a break while I’m taking the survey? Can I save my work and come back to it? – No problem! We recognize that the survey is long. The questions are designed to cover all aspects of living with RLS. You do NOT have to complete the survey in one sitting; you can close your browser and return using the same device to www.rls.org/odyssey to pick back up exactly where you left off. Just be sure to complete and submit the survey by midnight on Friday, October 23!

What do I need to do to make sure I submit the complete survey correctly? – After the final survey question you will be routed to an exit page thanking you for your participation. To ensure that your responses are recorded, make sure you click DONE at the bottom of this page; you will receive a “Success Page” to confirm that your responses have been received.

What if I don’t want to answer a question? – We understand that some questions may be difficult or uncomfortable to answer. You may choose to leave any questions blank you don’t wish to answer.

Is there a way to make the survey font size larger? – To zoom in on your computer screen, press the "Control +" keys on your keyboard (or "Command +" if you are using a Mac). You can also try adjusting the brightness of your computer and/or iPad screen. If you would prefer, we can mail a printed survey to your US address with a return envelope. Email maddie@rls.org to request a copy and be sure to include your name and mailing address.

What if I don’t find the right answer for me in the list of options for a multiple-choice question? – The RLS Patient Odyssey Survey II was written by medical professionals on our Scientific & Medical Advisory Board and includes questions from existing RLS validated questionnaires. One of the requirements when using validated questionnaires is that the questions must be presented exactly as written, with no changes to the original questionnaire. Just try to answer the question to the best of your ability, i.e., what is most reflective or representative of your RLS experience.

How do I enter dosages (invalid answer)? – Questions that ask for dosages require a numerical value only. Do not use letters (such as mg for milligrams). If you are instructed to take your medication several times per day, please provide the total dosage. For example, if your prescription states: gabapentin 600 mg TID PO, which translates to 600 mg three times daily per mouth, you would enter the number 1800. If a medication is used across multiple days, you can provide an average. If you are unsure you may email maddie@rls.org for assistance.

What should I do if I encounter technical difficulties? – Unfortunately, technical difficulties do happen. If this happens to you, you can contact us for a printed survey (see above), or take the survey directly on the Survey Monkey website (the survey development platform) here:

Who can I contact with questions? – For all other questions, comments and concerns, please email maddie@rls.org or call (512) 366-9109. Your input is very valuable to us!

East Carolina University associate professor receives patent for treating Restless Legs Syndrome

An East Carolina University faculty member’s latest patent may change the way Restless Legs Syndrome (RLS) is treated, leading to more effective care over a longer period of time for patients.

Stefan Clemens, an associate professor in the Brody School of Medicine’s Department of Physiology, was awarded U.S. Patent 10,751,327 on Aug. 25 for his novel treatment method for the treatment of RLS.

Restless Legs Syndrome is a nervous system disorder that affects between 5% and 8% of the population in the United States. Those suffering from RLS experience an uncontrollable urge to move their legs caused by an unpleasant sensation. While the exact cause of RLS is still unknown, the syndrome is typically treated with dopaminergic drugs — medications that replace or prevent the loss of dopamine — that have a high initial effect but over time lose their effectiveness.

“The problem is that patients on these dopaminergics eventually develop a side effect called augmentation,” Clemens said. “Their symptoms get worse while taking the current medication used for treatment.”

Classic RLS treatments act on a dopamine receptor known as D3 that has a suppressive effect in the nervous system. However, Clemens’ lab has shown in animal models that over time this medication leads to an increase of a different, excitatory receptor subtype, D1. This increase of the D1 receptor might be the cause of augmentation.

Clemens’ patent proposes a new treatment method that targets the increased D1 receptor levels in RLS patients suffering from augmentation, leading to reduced activation of D1 receptors while providing traditional therapy relief from RLS.

“Our lab postulates that this new compound will maintain long-term efficacy for RLS,” Clemens said. “If augmentation begins, we predict that we can reduce D1 receptor activation in patients and balance things back out, keeping the treatment effective.”

Clemens was awarded a grant from the North Carolina Biotechnology Center to run a small pilot study with a collaborator from the University of Houston using this new treatment method.

This work has gained the attention of a company that has interest in establishing a partnership where ECU’s patent rights may be used in combination with its existing drug formulation to bring relief to RLS patients suffering from augmentation.

Clemens added that the idea to apply for a patent came from ECU’s Office of Licensing and Commercialization.

“They not only brought the idea of patenting our research to my attention, but they also helped me through the process and handled all of the legal and technical aspects of filing a patent,” he said. “The patent would not have been issued without their help. I now know that it can be very beneficial to have experts in other areas come from different angles that make us think of other ways to use our work.”

Marti Van Scott, director of licensing and commercialization, said that finding commercialization opportunities for faculty research is an important bridge that brings science into the communities the university serves.

“It is a pleasure to work alongside our faculty to identify translational research opportunities that have potential to make a meaningful impact,” Van Scott said. “Licensing and commercialization works hard to identify skilled development partners to offer essential guidance for these translational activities. Whether it’s a new therapeutic or medical device, teaching or training method, or research tool, we are available to support the campus research and innovation ecosystem.”

While Clemens’ lab continues to work on its RLS treatment, Clemens said he’s also continuing to work on other medical treatments, including care for opioid pain tolerance.

Stefan Clemens, PhD, HdR, focuses his research on investigating the neural networks in the spinal cord, especially their role in neurological disorders, like RLS. He studies the role of dopamine in the spinal cord, and how the interactions between its different receptor subtypes may play a role in augmentation. At the RLS Foundation, Dr. Clemens serves on the Scientific and Medical Advisory Board where he chairs both the Brain Bank Committee and the Research Grant Committee.