GABA Pathways in Autism Spectrum Disorder (ASD)

• Status: Unknown status
• Trial end date: 2021-09-14
• Target enrollment: 0
• Participant gender: All

Summary

This study investigates the brain response to a single acute dose of AZD7325, a GABA-A positive allosteric modulator, compared to a single dose of placebo in adults with and without autism spectrum disorder.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: King's College London

Criteria

Inclusion Criteria

For all participants:

1. Calendar age above 18 years.

2. Able to give informed consent.

3. Not pregnant or breastfeeding.

4. Ideally prescription medication free during the 2-week period preceding a study visit. However, occasional use of over-the-counter medication (e.g. painkillers) on an as needed basis (and not on the day of study visit) may be permitted. In addition, regular prescription medication (use of a stable dose over the two months preceding participation) with a drug that does not affect glutamate or GABA directly may be permitted. Also permitted is topical medication without systemic exposure.

For individuals with ASD:

1. Diagnosis of ASD confirmed on the Autism Diagnostic Interview-Revised (ADI-R) if a relative is available and/or on the Autism Diagnostic Observation Schedule (ADOS-2).

For all relatives:

1. Aged under 18 years.

2. Does not know the participant personally at present or in their childhood.

Exclusion Criteria:

For all participants

1. History of allergy/idiosyncrasy to AZD7325 or chemically related compounds or excipients which may be employed in the study or to any other drug used in the past.

2. Subject has taken systemically (po, iv) any potent or moderate CYP3A4 or CYP2C9 inhibitor or inducer, 1 month prior to screening (topical or inhaled are permitted) such as: aprepitant, barbiturates, carbamazepine, clarithromycin, erythromycin, cyclosporine, diltiazem, efavirenz, fluconazole, HIV protease inhibitors, glucocorticoids, itraconazole (oral/IV), ketoconazole, nefazodone, nevirapine, phenytoin, pioglitazone, primidone, rifabutin, rifampicin, telithromycin, St. John's wort, verapamil.

3. Clinically relevant history or presence of any medical disorder, potentially interfering with this study.

4. Clinically relevant abnormality at screening as judged by the investigator.

5. History of or current abuse of drugs (including prescription medication) or alcohol or solvents.

6. Participation in a research study involving a pharmacological probe or drug trial within last month or more than four in the previous 12 months

7. Subjects with a history of epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousness.

8. Anyone with a history or examination which indicates laboratory testing is needed will be excluded from the study.

9. Intelligence Quotient below 70.

Reproductive safety: Male study participants who are sexually active should avoid procreation for 1 week after study drug administration. Avoidance of procreation can be through use of a highly effective contraception method by the study participant or by the partner. In this case, effective means of contraception are defined as tubal occlusion, copper banded intrauterine device, levonorgestrel medicated intra uterine system (e.g., Mirena), medroxyprogesterone injections (e.g. Depo-Provera), etonogestrel implants (e.g., Implanon, Norplan), normal and low dose combined oral contraceptive pills, norelgestromin / EE transdermal system, intravaginal device (e.g., EE and etonogestrel) and desogestrel (Cerazette).

Pregnancy or breastfeeding (is a routine exclusion for research MRI scanning). Female study participants must be willing to use one form of highly effective non-hormonal contraception for one week after study drug administration. This would include a vasectomised partner (sole partner), tubal occlusion, intrauterine system [IUS]/hormonal coil or copper containing intrauterine device or copper containing IUD, or true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Women should have been stable on their chosen method of birth control for a minimum of 2 months before entering the study. Participants must agree to undergo a pregnancy test prior to each administration of study drug.

For individuals with ASD:

1. ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome.

2. Currently treated for epilepsy.