Clinical Trials for Cerebral Amyloid Angiopathy
There are currently 5 ongoing clinical trials investigating treatments for cerebral amyloid angiopathy, a condition where protein deposits build up in the brain’s blood vessel walls. These studies are exploring medications, gene-targeting therapies, and nerve stimulation techniques across several countries including Finland, the Netherlands, and Iceland.
Clinical trial locations
- Finland
- Iceland
- Netherlands
Study on the Effects of Xenon and Oxygen on Brain Injury and Recovery in Patients with Aneurysmal Subarachnoid Hemorrhage in Intensive Care
This study, conducted in Finland, is investigating whether inhaled xenon gas can help protect the brain after aneurysmal subarachnoid hemorrhage, a type of bleeding that occurs when a blood vessel on the brain’s surface ruptures. While this trial focuses on a specific type of brain bleeding rather than the general condition, it is relevant to understanding blood vessel-related brain injuries.
Who can participate: Adults aged 18 and older who have experienced an aneurysmal subarachnoid hemorrhage confirmed by brain imaging are eligible. Participants must have a deteriorated consciousness level graded Hunt-Hess 3 to 5, be intubated for breathing support, and have a Glasgow Coma Scale score of 3 to 12 when not under muscle relaxants. The xenon treatment must begin within 6 hours of symptom onset, and consent must be obtained from a family member or legal representative since patients are typically unconscious.
Who cannot participate: The study excludes patients with uncontrolled serious infections, severe heart problems, recent stroke within the past 6 months, severe liver or kidney disease, pregnancy or breastfeeding, known allergy to xenon, participation in another clinical trial, mental health conditions that could interfere with the study, or a history of substance abuse.
Study focus: Researchers are examining whether xenon gas, administered through inhalation via a ventilator, can reduce brain injury and improve neurological outcomes. The study monitors changes in brain structure using MRI scans and tracks safety by comparing adverse events between those receiving xenon and those who do not. Follow-up continues for up to one year to assess long-term recovery.
Investigational treatment: Xenon is a noble gas with anesthetic properties being studied for its potential neuroprotective effects. It is believed to work by blocking certain receptors involved in brain cell death, thereby helping preserve brain function after hemorrhage.
Study on the Safety and Effects of ALN-APP for Patients with Cerebral Amyloid Angiopathy
Taking place in the Netherlands, this trial evaluates a medication called Mivelsiran, also known as ALN-APP, for treating the condition. This is a double-blind, placebo-controlled study, meaning some participants receive the actual medication while others receive an inactive substance, and neither patients nor researchers know who receives which treatment.
Who can participate: For sporadic cases, patients must be 50 years or older, while those with Dutch-type cerebral amyloid angiopathy must be at least 30 years old. All participants need a probable diagnosis based on medical history and MRI findings, with Dutch-type patients requiring confirmation of a specific E693Q APP gene mutation. Participants must have corrected vision of 20/50 or better for certain brain imaging tests, be able to undergo and tolerate MRI scans without metal implants or conditions making MRI intolerable, have a BMI between 18 and 34 kg/m², and be able to tolerate a lumbar puncture. A supportive study partner is required to attend visits and provide accurate information about the patient’s abilities.
Who cannot participate: The study excludes patients who have experienced brain bleeding, have new lobar cerebral microbleeds, or belong to vulnerable populations requiring special protection.
Study focus: The primary goal is to assess how effectively ALN-APP reduces the occurrence of new cerebral microbleeds, which are small areas of bleeding in the brain. Researchers will monitor changes using MRI scans and evaluate the medication’s safety and tolerability by tracking adverse events throughout the study period.
Investigational treatment: ALN-APP is administered through intrathecal injection, meaning it is delivered directly into the spinal fluid. It belongs to a class called RNA interference therapeutics, designed to reduce the production of amyloid proteins that accumulate in blood vessel walls and contribute to bleeding risk.
Study on Vagus Nerve Stimulation and Sodium Oxybate for Patients with Cerebral Amyloid Angiopathy
This Dutch study explores whether two different approaches, non-invasive vagus nerve stimulation and a medication called sodium oxybate, can help clear amyloid deposits from the brain’s blood vessels by activating the glymphatic system, the brain’s natural cleaning mechanism.
Who can participate: Eligibility varies by disease type. For Dutch-type cerebral amyloid angiopathy, patients must be at least 30 years old with either proven APP mutation or a history of at least one lobar brain bleed and positive family history. For probable sporadic cases, patients must be at least 50 years old and meet the Modified Boston criteria 2.0. For provisional cases, patients must be at least 50 years old with mostly lobar microbleeds and cortical superficial siderosis despite having deep hemorrhagic lesions. All participants should have had no more than two symptomatic brain bleeds, with the most recent occurring more than a year ago, and must have specific hemorrhagic or non-hemorrhagic markers visible on brain scans.
Who cannot participate: The study excludes individuals with severe allergic reactions to study treatments, significant uncontrolled heart problems, severe kidney or liver disease, current participation in another clinical trial, pregnancy or breastfeeding, drug or alcohol abuse within the past year, any other medical condition making participation unsafe, or inability to follow study procedures or attend required visits.
Study focus: Researchers will measure levels of amyloid-beta proteins in cerebrospinal fluid at baseline, 3 months, and 6 months using lumbar punctures. The study examines whether the treatments can stimulate the glymphatic system to remove amyloid deposits more effectively, potentially reducing the risk of future bleeding.
Investigational treatments: Low-sodium oxybate is an oral medication being tested for its ability to enhance the brain’s waste clearance process. It is a central nervous system depressant that modulates neurotransmitter activity. Non-invasive vagus nerve stimulation uses an external device to gently stimulate the vagus nerve through the skin, a form of neuromodulation therapy that may promote amyloid clearance without medication.
Study on the Safety and Effects of Acetylcysteine Amide for Patients Aged 12 and Over with Hereditary Cystatin C Amyloid Angiopathy
This Icelandic trial tests NPI-001, also known as acetylcysteine amide, in patients with Hereditary Cystatin C Amyloid Angiopathy, a specific genetic form of the condition. The medication is taken as a tablet by mouth.
Who can participate: Patients must be at least 12 years old and of Icelandic ancestry, with those aged 12-17 requiring safety board approval after reviewing adult safety data for at least 3 months. All participants must have the L68Q mutation in the cystatin C gene confirmed by genetic testing. They must agree to skin biopsies, blood tests, and brain MRI scans at baseline and during the study period up to 12 months. Patients with mild cognitive impairment can participate if they can follow study instructions. Women of childbearing potential and men capable of fathering children must agree to use acceptable birth control methods.
Who cannot participate: The study excludes those without an HCCAA diagnosis, anyone under age 12, individuals unable to take oral medication, those with severe allergic reactions to similar medications, patients with serious health conditions that might interfere with the study, pregnant or breastfeeding women, current participants in other clinical trials, those who had major surgery within the last 3 months, individuals with drug or alcohol abuse in the past year, and anyone unable to comply with study procedures.
Study focus: The study evaluates the safety and tolerability of NPI-001 over 12 months while examining its effectiveness in reducing the frequency of brain bleeding events. Researchers also measure changes in harmful protein complexes in the skin using advanced techniques, as these are linked to the disease process.
Investigational treatment: NPI-001 is a therapeutic agent taken orally that targets and aims to reduce amyloid-cystatin C complexes associated with the disease. It is being studied for its potential to decrease both cerebral bleeding events and the accumulation of disease-related protein deposits.
Study on the Safety and Effects of Acetylcysteine Amide for Patients Aged 12 and Over with Hereditary Cystatin C Amyloid Angiopathy
This is a second Icelandic trial also testing NPI-001 for Hereditary Cystatin C Amyloid Angiopathy, with similar design and objectives to the previous study.
Who can participate: Eligibility criteria are the same as the previous Icelandic trial. Patients must be at least 12 years old and of Icelandic ancestry, with the L68Q mutation in the cystatin C gene. Additionally, participants must have previously been found to have cystatin C/amyloid protein complexes in their skin and have mild cognitive impairment while still being able to follow study instructions. Agreement to undergo skin biopsies, blood tests, and brain MRI scans at baseline and throughout the study is required, along with appropriate birth control use.
Who cannot participate: Exclusion criteria mirror the previous trial, including those without HCCAA diagnosis, individuals under 12, anyone unable to take oral medication, those with allergies to the study medication or its ingredients, patients with severe liver or kidney problems, pregnant or breastfeeding women, recent participants in other clinical trials, individuals with certain mental health conditions affecting their ability to follow instructions, and those unable to provide informed consent.
Study focus: This study similarly evaluates safety, tolerability, and effectiveness of NPI-001 over up to 12 months. It monitors the frequency of cerebral bleeding events and uses various assessments including blood tests, skin biopsies, and brain MRI scans to track changes in the body and treatment effects. The trial is expected to continue until March 2025.
Investigational treatment: NPI-001 (AT-001) is administered orally and is currently in the clinical trial phase. It is designed to target the underlying mechanisms of Hereditary Cystatin C Amyloid Angiopathy at a molecular level, potentially altering the disease process and reducing cerebral bleeding events.
Summary
These five clinical trials represent diverse approaches to treating cerebral amyloid angiopathy and related conditions. The Netherlands hosts two studies exploring innovative treatments, including a gene-targeting therapy delivered directly into spinal fluid and a combination approach using nerve stimulation alongside medication to activate the brain’s cleaning system. Iceland focuses on a rare hereditary form of the condition with two trials testing an oral medication in patients as young as 12 years old, reflecting the genetic nature of this variant. Finland contributes a study examining xenon gas for brain protection after hemorrhage, though this focuses on a related but distinct condition.
A notable pattern is the emphasis on reducing brain bleeding events and clearing harmful protein deposits. Several trials require participants to undergo regular MRI scans and invasive procedures like lumbar punctures or skin biopsies to monitor treatment effects. The Dutch trials are particularly notable for testing novel approaches that aim to enhance the body’s natural mechanisms for clearing amyloid proteins. The Icelandic studies stand out for their focus on a specific genetic population and their inclusion of adolescent patients, reflecting the hereditary nature of that disease variant.
Most trials exclude patients with recent bleeding events, severe organ dysfunction, pregnancy, or participation in other studies. The requirement for study partners in some trials acknowledges the cognitive challenges patients may face. Overall, these studies reflect the complexity of treating a condition where protein buildup in blood vessel walls leads to bleeding risk, with researchers exploring multiple therapeutic strategies from gene silencing to metabolic enhancement.
