Treatment of alcohol dependence with an mTOR inhibitor: a safety and feasibility pilot study.

Not Applicable

• Conditions: Alcohol dependence; Mental Health - Addiction

• Registration Number: ACTRN12619000427178
• Lead Sponsor: Hunter New England Health Drug and Alcohol Clinical Services

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-15
• Last Update Posted: 15 July 2019

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1.Provide written, informed consent to participate in the study
2.Aged 18 to 65 years
3.Be treatment seeking for alcohol dependence
4.Meet DSM-5 criteria for moderate to severe alcohol use disorder (alcohol dependence) for at least twelve months
5.Self-report alcohol use of greater than or equal to 21 days out of the previous 28
6.Adequate liver function as shown by normal total bilirubin and albumin, ALT and AST less than or equal to 2.5 X upper limit of normal, INR less than or equal to 2
7.Adequate renal function, serum creatinine less than or equal to 1.5 X ULN
8.Patient must have adequate lipid profile, including fasting serum cholesterol, fasting glucose or fasting triglycerides
9.Full blood count and WBC differential within normal ranges
10.Adequate bone marrow function, including ANC and platelets
11.Females of child bearing potential must not be pregnant as confirmed by a negative pregnancy test (serum confirmed beta-hCG) or breastfeeding prior to study enrolment. Women of childbearing potential must agree to use adequate high-effective contraception for the duration of study participation and at least four months after the last dose of everolimus (e.g. oral contraception, intrauterine device, implant, combination of barrier methods, abstinence). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and 4 months after completion of everolimus administration.
12.Be willing and able to comply with requirements of study

Exclusion Criteria

1.Plans for immediate residential treatment/rehabilitation post withdrawal
2.Antidypsotropic (acamprosate, naltrexone, disulfiram) pharmacological treatment for alcohol dependence for more than 7 days in the previous month
3.Plans to commence antidypsotropic pharmacological treatment (acamprosate, naltrexone, disulfiram) for alcohol dependence during the study (inclusive of treatment and follow-up period)
4.History of complicated/severe alcohol withdrawal (e.g. alcohol withdrawal seizures, delirium).
5.Patients with a known hypersensitivity to everolimus or other rapalogues (sirolimus, temsirolimus)
6.Contraindication to study drug (everolimus): Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients
7.High or increasing C-reactive Protein, CRP levels =10mg/L
8.Systemic infection requiring therapy at study entry
9.Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. As lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx or medical reference text.
10.HIV-positive patients on combination antiretroviral therapy. These therapies have potential pharmacokinetic interactions with everolimus. Patients are also at increased risk of lethal infections when treated with marrow suppressive therapy.
11.Presence of another moderate-severe substance use disorder (other illicit or prescription drug dependence) with the exception of nicotine dependence, diagnosed by specialist clinical assessment against DSM-5 criteria, including urine drug screen. Already receiving study drug for any reason (e.g. kidney or cardiac allograft)
12.Patients who have had major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anaesthesia), or patients who may require major surgery during the course of the study.
13.Prior treatment with any investigational drug within the preceding 4 weeks.
14.Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone = 20 mg. Patients receiving these corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with Everolimus. Topical or inhaled corticosteroids are allowed.
15.Patients who have received immunization with attenuated live vaccines within one week of study entry or during study period.
16.Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
a.Symptomatic congestive heart failure of New York Heart Association Class III or IV.
b.Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease.
c.Severely impaired lung function as evidenced by:
(TLC) <50% predicted, OR (FVC) <50% predicted OR, (DLCO) <40% predicted
d.Uncontrolled diabetes/pre-diabetes as defined by fasting serum glucose >5.5mmol/L.
e.Active (acute or chronic) or uncontrolled severe infections.
f.Liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic p

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Intervention feasibility, namely administration of everolimus during the withdrawal period, as measured by:<br>Recruitment rate<br>Completion rate at end of treatment period<br>Adherence to everolimus[Day 14 of treatment (end of treatment)<br>Day 42 post treatment allocation (28 days after end of treatment)];Safety of everolimus during the withdrawal phase in participants with alcohol dependence as assessed by:<br>- Complete physical assessments by a physician <br>- Blood samples for safety analysis (full blood count, liver function, renal function, lipid profile and blood glucose)<br>- Adverse event log<br>- Participant diary<br>[Day 14 of treatment (end of treatment)<br>Day 42 post treatment allocation (28 days after end of treatment)]