I2PETPG - Imidazoline2 Binding Sites in a Group of Participants Diagnosed With AD (I2PETPG)
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|ClinicalTrials.gov Identifier: NCT02874820|
Recruitment Status : Terminated (Patient recruitment issues.)
First Posted : August 22, 2016
Last Update Posted : August 27, 2020
The imdazoline2 binding site (I2BS) is known to reside inside astrocytes. Changes in the numbers of I2BS in post mortem tissue has implicated them in a range of psychiatric conditions such as depression and addiction, along with neurodegenerative disorders such as Alzheimer's disease and Huntington's chorea. Preclinical studies have also demonstrated functional interactions with the opioid system, where I2BS ligands have been shown to affect tolerance to morphine and alleviate some of the morphine withdrawal syndrome in rats. Recently the I2BS and I2BS ligands have been shown to have some interesting analgesic effects in different models of pain.
The location of I2BS on astrocytic glial cells and the possibility that they may in some way regulate glial fibrillary acidic protein have led to increased interest into the role of I2BS and I2BS ligands in conditions characterised by marked gliosis. The number of I2BS has been shown to increase in Alzheimer's disease post mortem, and it has also been suggested that I2BS may be a marker for the severity and malignancy of human glioblastomas.
The lack of suitable imaging tools for the I2BS has meant that information regarding the number and distribution of I2BS in the brain has come from preclinical species and in vitro post-mortem studies. The recent development of [11C]BU99008 as a suitable PET ligand to quantify I2BS in vivo, enables the direct quantification of I2BS availability and regional distribution in the living human brain. In this study the investigators plan to utilise [11C]BU99008 to quantify the regional brain availability of I2BS in the human brain in vivo using PET.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Radiation: [11C]BU99008 Drug: Idazoxan||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||I2PETPG - Quantification and Localisation of Imidazoline2 Binding Sites in a Group of Participants Diagnosed With Alzheimer's Disease Using 11C-BU99008: a Positron Emission Tomography Study|
|Study Start Date :||July 2016|
|Actual Primary Completion Date :||March 2017|
|Actual Study Completion Date :||July 2017|
Experimental: Patient Group
Baseline PET scan followed by a blocked PET scan
Baseline and blocked scans
Idazoxan dose up to 80mg
- Density and distribution of Imidazoline 2 binding sites using either Total Volume of Distribution (VT) or Binding Potential (BP) [ Time Frame: 1 year ]The primary outcome of this study will be the determination of the regional density and distribution of the I2BS in human brain of participants with a diagnosis of early AD. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human. However, from our current study of this ligand in healthy volunteers this will probably be the Volume of distribution (Vt) derived from the 2 tissue compartment model (2TCM).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02874820
|Centre for Neuropsychopharmacology; Division of Brain Sciences; Imperial College London; Burlington Danes Building; Hammersmith Hospital campus; 160 Du Cane Road|
|London, United Kingdom, W12 0NN|
|Principal Investigator:||David J Nutt, MD||Director of Centre for Neuropsychopharmacology, Imperial College London|