I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: Male

Summary

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 and a novel I2BS ligand, CR4056, is currently undergoing Phase II clinical trials as a novel treatment for neuropathic pain and acute non- specific pain states.

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Imperial College London
• Collaborator: GlaxoSmithKline
• Treatments: Idazoxan; Isocarboxazid

Criteria

Inclusion Criteria:

• Male between 40 and 65 years at the time of signing the informed consent Non-smoker

• Willing to comply with protocol and lifestyle restrictions

• Excellent understanding of English (for questionnaires)

• Subject is ambulant and capable of attending a PET scan visit as an outpatient.

• Subjects with female partners of child-bearing potential must agree to use one of the contraception methods permitted by the study. This criterion must be followed from after the first PET Scan until after the follow-up contact.

• Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test.

• Body weight ≥50 kg.

• Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, objective physiological measures, previous laboratory studies, and other tests.

• Successful completion of the CAMCOG.

Exclusion Criteria:

• Current or past history of major psychiatric disorder

• Current or past history of substance use disorder

• Clinically significant brain injury or abnormality

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• History of or suffers from claustrophobia or subject feels unable to lie flat and still on their back for a period of up to 2 hours in the PET/CT scanner.

• Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure resulting in radiation exposure greater than 10 mSv over the past 3 years or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the subject receives a direct benefit is not included in these calculations.

• Previous inclusion in a research and/or medical protocol involving study medication within the last 3 months

• In the opinion of the study team they are unlikely to comply with the study protocol and restrictions that it imposes.

• Contraindications for subjects undergoing an MR scan (including but not limited to metal implants pacemakers, etc.)