Evaluation of [18F] FMH3 and PET as a Marker of Histamine-3 Receptor Activity in Subjects With AD Compared w/ HC (FMH3)

An Exploratory, Open-label, Non-randomized Phase 0 Study to Evaluate [18F]-FMH3 by Positron Emission Tomography (PET) for Quantization of the Receptor Histamine-3 in Human

The underlying goal of this study is to assess [18F]-FMH3 PET imaging as a tool to evaluate the activity of the H3 receptor in the brain of Alzheimer Disease (AD) research participants

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: [18F]-FMH3

Detailed Description

Approximately 10 subjects with Alzheimer disease (AD) and 8 healthy control (HC)subjects will be recruited to participate in this study. All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations. Subjects will be asked to undergo a bolus injection of [18F]-FMH3. Subjects will undergo serial PET imaging scans and plasma sampling for measurement of [18F]-FMH3 in plasma (both protein bound and free) over a period of up to 8 hours. The primary imaging outcome measure will be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the radioligand, [18F]-FMH3.

At least 2 weeks following the initial imaging visit, subjects may be asked to return for a second injection and scanning procedure to evaluate the reproducibility of the imaging measure using this procedure. Subjects may decline to participate in the second scan.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute For Neurodegenerative Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The following criteria will be met for inclusion of AD subjects in this study:

• The participant is 50 years or older.
• Written informed consent is obtained.
• Participants have a clinical diagnosis of probable Alzheimer disease in accordance with the DSM-IV-TR and according to (NINCDS/ADRDA) criteria.
• Clinical Dementia Rating Scale score ≤ 2.
• Modified Hachinski Ischemia Scale score of ≤ 4.
• Geriatric Depression Scale (GDS) ≤ 10.
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of [18F]-FMH3 injection.

The following criteria will be met for inclusion of healthy control subjects in this study:

• The participant is 18 years or older.
• Written informed consent is obtained.
• Negative history of neurological or psychiatric illness based on evaluation by a research physician.
• Clinical Dementia Rating score = 0.
• For females, non-child bearing potential a negative urine or blood pregnancy test on day of [18F]-FMH3 injection.

Exclusion Criteria:

Alzheimer's subjects will be excluded from participation for the following reasons:

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
• The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.

Healthy control subjects will be excluded from participation for the following reasons:

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
• The subject has any contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]-FMH3-01 PET Imaging; Subjects will be injected with up to 5 mCi and not to exceed 5.5mCi (not >10% of 5 mCi limit) or 2 ug of [18F]-FMH3, whichever is greatest.	Drug: [18F]-FMH3; Subjects will be injected with up to 5 mCi and not to exceed 5.5mCi (not >10% of 5 mCi limit) or 2 ug of [18F]-FMH3, whichever is greatest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the dynamic uptake and washout of 18F-FMH3	To assess the dynamic uptake and washout of [18F]-FMH3, an imaging marker targeting the histamine H3 receptor in brain, using positron emission tomography (PET) in subjects with Alzheimer (AD) and healthy controls (HC).	1 year

Collaborators and Investigators

• Sponsor: Institute for Neurodegenerative Disorders

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: December 28, 2010
• First Submitted That Met QC Criteria: December 28, 2010
• First Posted (Estimate): December 29, 2010

Study Record Updates

• Last Update Posted (Estimate): November 11, 2013
• Last Update Submitted That Met QC Criteria: November 8, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Alzheimer; AD
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: FMH3-01