In Vivo Quantification of Hsp90 in the Human Brain in Healthy Aging and Neurodegeneration Using the Novel PET Radioligand [11C]HSP990

Plain English Summary

Quantification of Hsp90 in the Human Brain is a Not Applicable clinical trial sponsored by Universitaire Ziekenhuizen KU Leuven studying Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS). This study uses a new imaging agent called [11C]HSP990 with PET scans to measure levels of a protein called Hsp90 in the brain. It is looking for healthy volunteers and individuals with Parkinson's Disease, Alzheimer's Disease, or Amyotrophic Lateral Sclerosis (ALS). Participation involves undergoing PET scans, which are a type of medical imaging. Currently, there are no direct alternatives for measuring Hsp90 levels in the brain using this specific imaging method. The trial aims to enroll 48 participants.

Official Summary

This study tests the radiolabeled molecule ("tracer"), \[¹¹C\]HSP990, using positron emission tomography (PET) imaging to assess whether it can be used to measure levels of Heat Shock Protein 90 (Hsp90). The protein Hsp90 plays an important role in how proteins in the brain fold into their three-dimensional structure and how this protein helps maintain cellular homeostasis. Since neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by disrupted three-dimensional protein folding resulting in protein aggregation, we also aim to measure Hsp90 levels in patients with these conditions. \[¹¹C\]HSP990 is a promising tracer for this purpose and has already been extensively tested in animal models with safe and favorable results. The investigator now aims to evaluate this tracer in the human brain in healthy volunteers as well as in patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. The investigator expects that Hsp90 protein levels will be present at reduced concentrations in patients, possibly in different brain regions depending on the distribution of the disease-causing proteins associated with these disorders. Since the discovery of the important role of Hsp90 in neurodegenerative diseases, several candidate drugs targeting Hsp90 have been developed in recent years. The imaging method used in this study may support the development of Hsp90-targeting medications by enabling measurement of Hsp90 levels in the brain and assessment of the effects of these drugs.

Who Can Participate

Here is what you need to know about eligibility for this trial. Healthy individuals aged 18-70 can participate if they are in good health and have no major neurological or psychiatric conditions. Patients with Parkinson's Disease, Alzheimer's Disease, or ALS are eligible if they meet specific diagnostic criteria and are between 45-85 years old (or 20-85 for ALS). Individuals with significant medical conditions like heart, liver, or kidney disease, or a history of cancer, may not be eligible. People who cannot tolerate MRI scans or lie still for extended periods are excluded. This trial is studying Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how much Hsp90 protein can be detected in the brain using the new imaging technique, which could indicate the health of brain cells and how diseases are progressing. The specific primary outcome measures are: Quantification of HSP90 in the human brain (This will be assessed right after each scan in cohort 2 and 3. (Estimated visit lenght in cohort 2 will be 4 hours for each scanning procedure. In cohort 3 this will be optimized based on the results of cohort 2.)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial is important because it aims to develop a new way to measure Hsp90 protein levels in the brain, which could help in understanding and developing treatments for neurodegenerative diseases li This research targets Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), where improved treatment options are needed.

Investor Insight

This trial signals potential advancements in diagnostic tools for neurodegenerative diseases, potentially opening avenues for targeted therapies and improving the precision of drug development in a si

Is This Trial Right for Me?

Ask your doctor if this study is a good fit for your condition and if you meet the eligibility requirements. Participation involves several PET scans, which are non-invasive imaging procedures, and potentially MRI scans. You will need to provide informed consent and may need to use specific birth control methods if you are of childbearing potential. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 48 participants

Interventions

• OTHER: [11C]HSP990 PET dosimetry — 120 minute whole body PET/CT scan with \[11C\]HSP990 radiotracer
• OTHER: [11C]HSP990 PET test-retest — 2 120-minute brain PET scan with \[11C\]HSP990 radiotracer
• OTHER: [11C]HSP990 simplified scan protocol — Simplified quantitative \[11C\]HSP990 PET scan as will be determined in part 2.

Primary Outcomes

• Quantification of HSP90 in the human brain (This will be assessed right after each scan in cohort 2 and 3. (Estimated visit lenght in cohort 2 will be 4 hours for each scanning procedure. In cohort 3 this will be optimized based on the results of cohort 2.))

Secondary Outcomes

• To assess the safety and clinical tolerance of [11C]HSP990 administration. (From enrollment until 1 week after completion of scan.)
• To determine the radiation dosimetry of [11C]HSP990 in humans. (This will be assessed right after each scan in cohort 1. (Estimated lenght of the scanning visit is 4 hours.))
• To determine the optimal brain tracer kinetic modelling approach and test-retest variation (TRV) for [11C]HSP990 brain PET in humans. (This will be assessed right after each scan in cohort 2. (Estimated lenght of each scanning visit is 4 hours.))
• To determine the optimal imaging protocol for quantifying Hsp90 levels in human brain using [11C]HSP990 and develop if possible, a simplified imaging protocol or patient comfort. (This will be assessed right after each scan in cohort 2. (Estimated lenght of the scanning visit is 4 hours.))
• To assess age-dependency of Hsp90 levels in healthy human brain using [11C]HSP990 (This will be assessed right after each scan in cohort 2 and 3. (Estimated visit lenght in cohort 2 will be 4 hours for each scanning procedure. In cohort 3 this will be optimized based on the results of cohort 2.))

Full Eligibility Criteria

Inclusion Criteria:

Healthy controls

* Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
* Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
* Male or female subjects, age between 18-55 (Part 1, n = 3), 18-40 (Part II, n = 5) or 40-70 (Part III, 40-55 n = 5, 55-70 n = 5) years old.
* Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs, clinical laboratory test and urinalysis.
* No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment (SCL-90).
* (Part II and III only: ) In subjects \< 60 years of age, a normal structural MRI scan as assessed by expert radiologist. In subjects \>= 60 years of age white matter hyperintensities corresponding to a white matter lesion (WML) Fazekas score \< 2 on the Age-Related White Matter changes scale are acceptable

Parkinson's disease

* Age 45-85 years.
* Patient has clinically established PD based on the Movement Disorder Society (MDS) diagnostic criteria and is in Hoehn-Yahr stage I-III in the "on" medication state
* Patient has had a previous abnormal DaT-scan confirming the clinical diagnosis.
* Patient is able to understand the patient information brochure and give written informed consent

Alzheimer's disease

* Age 45-85 years.
* MoCA score \< 26
* Patient has a diagnosis of probable AD with evidence of the AD pathophysiological process (amyloid PET scan or CSF determination) according to the consensus criteria \[McKahn et al 2011, Alzh Dement\].
* Patient is able to understand the patient information brochure and give written informed consent.

Amyotrophic lateral sclerosis

* Age 20-85 years.
* Subjects will be recruited at the Neurology department of University Hospitals Leuven and must meet revised El Escorial Criteria and Awaji-Shima criteria for at least possible ALS.
* Patient is able to understand the patient information brochure and give written informed consent.

Exclusion Criteria:

Healthy controls

* Participant has a history of any major disease that may interfere with the investigations or make the subject unfit for participation according to the interpretation by the investigator (especially diabetes mellitus, heart disease, liver and kidney disease, or most forms of cancer).
* Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial .
* Participation in an interventional Trial with an investigational medicinal product (IMP) or device.
* Evidence of cognitive impairment.
* Subject has a history or evidence of psychiatric disease.
* Subject has renal impairment with eGFR \< 60 ml/min.
* Subject is currently a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse.
* (Part II and III only: ) Subject has a contra-indication for MRI scanning.
* Subject has a known hypersensitivity to any of the excipients that are present in the radiopharmaceutical preparations or to any of the excipients listed in the IMPD for \[11C\]HSP990.
* Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures. Subject cannot lie still for at least 70 minutes inside a scanner.
* Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e., weightlifting, running, bicycling) from the time of the pre-study visit until the end of scanning;
* Subject does not understand the study procedures.
* Subject is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator.
* Subject is pregnant (according to Ulti Med hCG urine test) or is breastfeeding.
* Subject is a woman of childbearing potential who does not agree to apply appropriate contraception methods during study participation and continues to do so for at least 6 months after study completion. For WOCBP: contraception methods with a relatively high Pearl index (natural methods, minipill outside postpartum period, spermicides or condoms in monocontraception or no usage of contraception when sexually active) are not accepted.
* Subject is a man with a pregnant or non-pregnant WOCBP partner, who does not agree to use a condom and continue to do so until 90 days after study completion. In addition, the non-pregnant WOCBP partner should use a highly effective metho

Trial Locations

• UZ Leuven, Leuven, Vlaam-Brabant, Belgium

Frequently Asked Questions

Related Conditions

• Parkinson's Disease
• Alzheimer's Disease
• Amyotrophic Lateral Sclerosis (ALS)
• Neurodegeneration
• Protein Folding Disorders
• Brain Imaging
• Radiopharmaceuticals
• Neurology
• Geriatrics
• Oncology (due to exclusion criteria related to cancer history)

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