Effect of MIFepristone on COGnitive impairment in alcoholics

• Register: ISRCTN
• Last refreshed on: 28 September 2020
• Main ID: ISRCTN54001953
• Date of registration: 29/09/2011
• Prospective Registration: Yes
• Primary sponsor: King's College London (UK)
• Public title: Effect of MIFepristone on COGnitive impairment in alcoholics
• Scientific title: Glucocorticoid receptor antagonism and cognition in alcoholics
• Date of first enrolment: 01/10/2011
• Target sample size: 120
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN54001953
• Study type: Interventional
• Study design: Randomised; Interventional; Design type: Treatment (Treatment)
• Phase: Phase III

Countries of recruitment

United Kingdom

Contacts

• Name: Hilary Little

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of alcohol dependence by DSM-IV for at least 5 years
2. Male
3. Aged under 60
4. Willingness to provide informed consent

The study will be limited to males because of the progesterone antagonist properties of mifepristone. The minimum duration of dependence will optimise incidence of cognitive deficits, whilst the upper age limit will minimise the contribution of age-related deficits.

Exclusion criteria:
The following conditions affect HPA function and are common in the alcoholic population:
1. Depressive disorders
2. Smoking
3. Hypertension
4. Obesity
5. Liver disease
6. Kidney disease
7. Post traumatic stress disorder
8. Mental illness
9. Brain damage
10. Comorbid substance dependence

While we shall make the exclusions detailed below, to omit all these disorders would render the majority of the inpatient subject population ineligible, which would affect the external validity of the research and limit the examination of the role of the glucocorticoid Type II receptor. We therefore propose to include those with less severe forms of these disorders, to document the symptomatology carefully, and to analyze possible influences of these disorders on the variables under study.

Exclusion criteria:
1.Clinical diagnosis of a neuroendocrine disorder
2. Liver damage, determined by alanine aminotransferase (ALT) activity of more than 2.5 x normal range
3. Renal dysfunction
4. Psychotic disorder that would limit valid provision of informed consent (ICD-10 diagnosis from the CIDI)
5. Severe brain damage or severe mental impairment
6. Diagnosis of severe physical illness that would preclude participation (e.g. terminal illness)
7. Inability to understand sufficient english to take understand the information needed for the cognitive testing
8. Female gender
9. Patients with Korsakoff's/Wernicke's syndromes (less than 2% in our Treatment Unit) will not be included because the cognitive deficits are considered to be permanent and due primarily to thiamine deficiency
10. Porphyria
11. Asthma
12. Owing to potential interactions with mifepristone, participants taking the following drugs will be excluded: ketoconazole, itraconazole, metronodazole, miconazole, erythromycin, clarithromycin, troleandomycin, rifampin, rifabutin, norfloxacin, nefadazone, nelfinavir, ritonavir, saquinavir, omeprazole, zafirlukast, fluvoxamine, quinine, phenytoin, phenobarbital, primadone, carbamazepine, troglitazone, amiodarone, warfarin, indomethacin, aspirin, corticosteroids or St John's Wort.
Consumption of grapefruit juice is also contraindicated during mifepristone treatment


Age minimum:
Age maximum:
Gender: Male

Health Condition(s) or Problem(s) studied

Addictions; Disease: Addictive Substances alcohol
Mental and Behavioural Disorders
Mental and behavioural disorders: alcoholism

Intervention(s)

There will be 120 participants, 60 in each treatment group. Mifepristone or placebo will be administered for 14 days starting on the first day of admission. Mifepristone, Adjunctive treatment with mifepristone (600 mg/day for 7 days followed by 400mg/day for 7 days) versus placebo. Cognitive testing will be conducted at the end of treatment. Follow-up contacts will be 3, 6 and 12 months to determine whether each participants has maintained abstinence or relapsed back into alcohol drinking.

Follow Up Length: 12 month(s); Study

Primary Outcome(s)

Cognitive performance; Timepoint(s): One week after cessation of treatment

Secondary Outcome(s)

Depression symptoms; Timepoint(s): Baseline and weekly for trial duration

Secondary ID(s)

9272

2009-015837-55

Source(s) of Monetary Support

Medical Research Council (MRC) (UK)

Ethics review

Status:
Approval date:
Contact:

ref: 10/H0808/7

Results

• Results available: Yes
• Date Completed: 31/12/2014