The Tolerability and Effects of AZD0530 in Individuals With or Without a Family History of Alcoholism

Alcoholism Clinical Trial

Official title:

A Phase One Study Investigating the Tolerability and Effects of AZD0530 on Functional Neuroimaging Responses in Individuals With or Without a Family History of Alcoholism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02262026
• Other study ID #: 1503015528
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2014
• Est. completion date: April 26, 2019

Study information

• Verified date: February 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Functional neuroimaging of alcoholism vulnerability: glutamate, reward, impulsivity, and Pavlovian-to-instrumental transfer (PIT), part II Saracatinib

Description:

To assess the effect of oral AZ D0530 at various doses on neuroimaging parameters associated with various forms of impulsivity mediated through glutamate-dopamine interactions, as ascertained through functional magnetic resonance imaging. -- --NOTE-- AZD0530 dosage of 50mg was discontinued by manufacturer. Adjustments were made to account for the removal of the 50mg dosage in all arms of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 26, 2019
• Est. primary completion date: April 26, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Clear History of a father having a history of alcoholism, OR a mother AND another 1st or 2nd degree relative having a history of alcoholism, OR no 1st or 2nd degree relatives with alcoholism or substance abuse

Exclusion Criteria:

1. Current diagnosis of DSM-IV-TR Axis I disorder, or past diagnosis of any substance use disorder or moderate alcohol use disorder

2. Report of psychotic disorder in a 1º relative

3. Auditory or visual impairment that interferes with test taking

4. History of prenatal exposure to alcohol plus currently meeting criteria for features of fetal alcohol syndrome

5. Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English >grade 1

6. Mental retardation (Full Scale IQ<70) using 2 WASI subtests for IQ estimate

7. Traumatic brain injury with loss of consciousness > 30 minutes, or concussion in last 30 days

8. Presence or history of any medical/neurologic illness that may affect brain physiology (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural MRI (all structural scans are read by a licensed radiologist)

9. Current pregnancy (all females will be tested with urine screens on the day of MRI and prior to each phase of drug treatment)

10. Positive urine screen for the presence of marijuana, cocaine, opiates or breath screen to detect the presence of alcohol, administered at each lab visit.

11. Inability to comprehend the consent form appropriately

12. Ferromagnetic metal devices, clips or fragments in body (orbital x-ray performed if needed).

13. Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.

14. Current use of the following medications (CYP3A4 substrates whose metabolism may be slowed by AZD0530): carbamazepine, colchicine, cyclosporine, disopyramide, fluticasone, quinidine, vinblastine, vincristine, nifedipine. Patients taking sildenafil, tadalafil, and vardenafil will be advised to stop taking these medications for the duration of the trial. Patients cannot take the following drugs which inhibit the CYP3A4 isoenzyme: cimetidine, cyclosporine, danazol, fluconazole, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole, macrolides, miconazole, nefazodone, omeprazole, ritonavir, and verapamil, aromatase inhibitors, docetaxel

15. Neutropenia defined as absolute neutrophils count of <1,500/microliter.

16. Thrombocytopenia defined as platelet count <100x103/microliter.

17. AST, ALT, total bilirubin >1.5 times upper normal; serum creatinine, >2 time upper normal limit, total bilirubin>1.5 times ULN; Serum creatinine >2.0 times ULN.

18. History of interstitial lung disease.

Related Conditions & MeSH terms

• Alcoholism

Intervention

Drug:
• 125 mg AZD0530
Randomized to receive 125 mg of AZD0530
• 50 mg AZD0530
Randomized to receive 50 mg of AZD0530
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Hartford Hospital	Hartford	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BOLD activation during A1 phase	BOLD activation during the A1 phase of the MRI Monetary Incentive Delay task	4 Hours post medication administration
Secondary	BOLD signal activation in the anterior cingulate cortex(ACC)	BOLD signal activation in the anterior cingulate cortex (ACC) observed during False Alarms of the GoNoGo Task	4 Hours post medication administration