18F-mFBG Cardiac Uptake With Lewy Body Dementia

Official title

An Open-Label, Exploratory, Phase 2 Scintigraphy Study Evaluating 18F-mFBG for Imaging Myocardial Sympathetic Innervation in Subjects With and Without Lewy Body Diseases

Overview

This is a Phase 2 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for quantification of the effect of neurodegenerative diseases on myocardial sympathetic innervation. Effectiveness of 18F-mFBG imaging of the heart will be judged in terms of the quantitative difference between results for subjects with Lewy body and non-Lewy body neurologic disease as compared to historical data for healthy control subjects.

Detailed description

Over the past 40 years, significant efforts have been made to develop imaging techniques to monitor the heart's autonomic nervous system, particularly the sympathetic system and its key neurohormone, norepinephrine (NE). In heart disease, NE function is often disrupted, leading to reduced NE uptake and transporter expression, which can contribute to heart failure, arrhythmias, and sudden cardiac death. Similar NE system dysfunction is also seen in neurological conditions like pure autonomic failure (PAF), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB), which are associated with Lewy body deposits in the nervous system. Most research on myocardial sympathetic neuronal imaging has focused on NE-analogues labeled with gamma- or positron-emitting radioisotopes. The most commonly studied agent is 123I-mIBG, which provides semi-quantitative data. However, its results depend heavily on imaging equipment and techniques, making global standardization difficult. Additionally, accurately measuring myocardial uptake and clearance is challenging with SPECT, even when using correction methods. While most cardiac mIBG research has focused on patients with heart disease, a significant number of studies have examined the effect of Lewy body disease on myocardial sympathetic innervation. These studies have consistently demonstrated a significant reduction in myocardial mIBG uptake. mIBG scintigraphy has high sensitivity (88%) and specificity (85%) for distinguishing Parkinson's disease (PD) from other Parkinsonism disorders. In a study of 123I-mIBG scans, the heart/mediastinum ratio (HMR) showed 68.9% sensitivity and 89.1% specificity for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Neurologists and movement disorder specialists find mIBG imaging helpful for assessing suspected Lewy body disease. Positron-emission tomography (PET) is the preferred method for high-resolution imaging of cellular functions. This study uses 18F-meta-fluorobenzylguanidine (18F-mFBG), a new radiopharmaceutical similar in structure to 123I-mIBG but with faster pharmacokinetics and elimination. Compared to 123I-mIBG, 18F-mFBG clears more quickly from the blood and target organs, resulting in better heart imaging quality and reliability. While most research on 18F-mFBG has focused on imaging neural crest tumors like neuroblastoma and pheochromocytoma, its performance is expected to be strong based on prior experience with 123I-mIBG. With the greater sensitivity and resolution of PET imaging compared to planar and SPECT techniques, it is expected that 18F-mFBG imaging will be less procedure-dependent than 123I-mIBG and provide the reliable and reproducible quantitative accuracy necessary to support use of this agent for clinical patient studies.

Interventions

• Drug 18F-MFBG
  Intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG followed by whole body PET imaging.

Primary outcome measures

• Cohort 1: Quantify the extent and degree of global and regional reduced 18F-mFBG myocardial uptake on PET/CT (or PET/MR) of subjects with known or presumed Lewy body disease (Parkinson's disease (PD) and Lewy body dementia (LBD)). [Time frame: 6 months]

Secondary outcome measures (3)

• Cohorts 1 and 2: Quantify 18F-mFBG whole-body activity distribution in Lewy body disease subjects (voxel, regional, and global basis) at 30-minutes post-administration [Time frame: 6 months]
• Cohort 1 and 2: 18F-mFBG PET quantitative assessment at 60 minutes [Time frame: 6 months]
• Cohorts 1 and 2: Global myocardial 18F-mFBG activity in Lewy body disease subjects compared to non-Lewy body disease subjects. [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• 1\. ≥18 years of age at study entry. 2. Able and willing to comply with study procedures and signed and dated informed consent is obtained.

3\. A male or a female who is either surgically sterile (has had a documented bilateral oophorectomy and/or hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a serum pregnancy test performed at screening is negative.

4\. All subjects: Judged clinically stable for at least 30 days before enrolment into the study and remains stable to the time of the study imaging procedure.

For Lewy body disease subjects (Study Cohort I):

5\. The subject has a diagnosis of either PD or DLB based on accepted clinical criteria at least 6 months before enrollment into the study.

For non-Lewy body disease subjects (Study Cohort II):

6\. The subject has a diagnosis of neurological or neurodegenerative disease for which neither PD nor DLB is judged likely by a neurologist based on accepted clinical and imaging criteria.

Exclusion criteria

• 1\. Previously entered into this study or has participated in any other investigational product or medical device study within 30 days of enrollment.

2\. History or suspicion of significant allergic reaction or anaphylaxis to any components of the 18F-mFBG imaging agent.

3\. Presents with any other clinically active, serious, life-threatening disease with a life expectancy of less than 1 year or where participation in the study might compromise the management of the subject or other reason that in the judgment of the investigator(s) makes the subject unsuitable for participation in the study.

4\. Documented ischemic heart disease (prior myocardial infarction, unstable angina, etc) or a diagnosis of heart failure of ischemic or non-ischemic etiology.

5\. Serious non-cardiac medical condition associated with significant elevation of plasma catecholamines including pheochromocytoma.

6\. The subject is claustrophobic or has a movement disorder that prevents him/her from lying still in a supine position for up to 20 minutes.

7\. Renal insufficiency (serum creatinine >3.0 mg/dL). 8. Uses medications that are known to interfere with uptake of NET-dependent agents and these medications cannot be safely withheld 24 hours before study procedures.

9\. Participated in a research study using ionizing radiation in the previous 12 months such that participation in the study might result in a total effective dose from research procedures exceeding 50 milliSieverts during that time interval.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Houston Methodist Neurological Institute — Houston

Identifiers

NCT: NCT07176286 · IRP101-231

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗