Oral Ketamine in Resistant Alcohol Use Disorder: A Multi-centric Single-blind Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Change in the relapse rates in patients receiving oral ketamine against those receiving oral midazolam. The relapse rates will be calculated based on the primary endpoint of a heavy drinking episode within three months of discharge from hospital. The secondary endpoints of time to relapse, number of relapses and treatment discontinuation will be consodered.
研究概览
简要总结
1 Background
Alcohol use disorder (AUD) is responsible for substantial morbidity and mortality in our country. Currently, available pharmacological and psychosocial treatment options fail to benefit a sizeable number of patients. Ketamine has emerged as an effective treatment for resistant depression and has preliminary evidence in AUD. However, currently used protocols are impractical due to the need for an anaesthetist for parenteral ketamine dose and cost-ineffective, patent-protected nasal spray. Ketamine is absorbed when used orally, and there is emerging evidence that metabolites generated during first-pass hepatic metabolism are active.
2 Novelty
Therefore, we propose that oral ketamine therapy is a viable option and should be explored. This will be the first study to use oral ketamine for a substance use disorder. We will also provide pharmacokinetic data of oral ketamine in adults, which is currently unavailable.
3 Objectives
To evaluate the efficacy and safety of oral doses of ketamine in improving outcome and severity measures of resistant AUD.
4 Methods
Randomized, double-blind, placebo-controlled trial to test the efficacy of orally administered ketamine in preventing relapse to heavy drinking, when used as a maintenance treatment given weekly. We will recruit AUD in-patients (N = 116, 1:1 randomization) who have not responded to treatment and randomize them to receive either ketamine (150-250 mg per oral) or a psychoactive placebo (midazolam 10-15 mg per oral) every week. We will also measure the blood concentration of ketamine and its metabolites to make a population pharmacokinetic model.
5 Expected outcomes
At the end of the study, we should be able to provide efficacy, safety and pharmacokinetic data of oral ketamine treatment in AUD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Either gender.
- •Age between 18 to 65 years.
- •Diagnosis of Alcohol Use Disorder (AUD)- Severe, diagnosed by a psychiatrist per Diagnostic and Statistical Manual 5 TR (DSM-V TR).
- •Severity of Alcohol Dependence Questionnaire (SADQ) score of 31 or more signifying severe dependence.
- •Inadequate response to standard treatment for AUD defined as follows (both criteria should be met): • Relapse to heavy drinking within three months of discharge in at least one previous admission.
- •This is based on the DSM-5 TR definition of early remission in AUD.
- •â€¢ Failed trials of at least one of the standard or off-label medications (Acamprosate, Baclofen, Topiramate, Naltrexone, Disulfiram) as evidenced by relapse to heavy drinking while on treatment or following non-compliance.
- •Willingness to come for fortnightly sessions and for blood tests.
- •For females of reproductive age, willingness to take effective contraception from the day of signing the consent form until six weeks after treatment discontinuation.
排除标准
- •Currently taking any other relapse prevention medication
- •Uncontrolled hypertension (systolic 140 mm Hg or greater and diastolic 90 mm Hg or greater).
- •Body mass index (BMI) more than
- •History or presence of a psychotic illness
- •Current or past history of recreational use of any prescription drug.
- •Current or past history of any other SUD except nicotine and cannabis.
- •Intellectual disability, sensory impairment or uncommunicative patients where obtaining consent and assessment of craving, adverse effects are precluded.
- •Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73 m2 as calculated using Modification of Diet in Renal Disease formula (MDRD).
- •Severe Alcoholic hepatitis or end-stage liver disease as defined by a MELD score (Model of end-stage liver disease) more than or equal to
- •Unstable angina.
- •History of intracranial mass lesion or glaucoma
- •History of an allergic reaction to ketamine.
- •Pregnant or breastfeeding currently.
结局指标
主要结局
Change in the relapse rates in patients receiving oral ketamine against those receiving oral midazolam. The relapse rates will be calculated based on the primary endpoint of a heavy drinking episode within three months of discharge from hospital. The secondary endpoints of time to relapse, number of relapses and treatment discontinuation will be consodered.
时间窗: T0 is the time of first treatment session. | T1 is at 2 weeks from T0. | T2 is at 4 weeks from T0. | T3 is at 6 weeks from T0. | T4 is at 8 weeks from T0. | T5 is at 10 weeks from T0. | T6 is at 12 weeks from T0.
次要结局
- The pharmacokinetic parameters of oral ketamine in adults with a population pharmacokinetic framework as it can handle unbalanced (unequal number of samples given by different subjects), unstructured (variable time of collection of samples with respect to drug administration) and sparse data.(T0 is the time of first ketamine session.)
- The tolerability and safety of oral ketamine in alcoholo use disorder. This will be assessed using a multimonitor with breathing rate, heart rate, non-invasive blood pressure, and SpO2 probe during the sessions. Other scales used will be: 1) Clinician-Administered Dissociative States Scale (CADSS) before the session and at 30 minutes after ingestion, 2) 4 items positive sub-scale of Brief Psychiatric Rating Scale (BPRS) before and at 60 minutes after ingestion, 3) Observer’s assessment of alertness/sedation scale (OAASS) before, at 30 minutes and at 60 minutes of ingestion, 4) Bladder Pain Interstitial Cystitis Symptom Score (BPICSS) before each session starting with the second session, 5) 5 Item, Likert scale version of Drug Effect Questionnaire (DEQ) at 30 minutes after ingestion in each session, 6) Assessment for vomiting, nausea, retching, 7) Other treatment-emergent adverse event(T0 is the time of first treatment session.)
- The mediators of change in the drinking behaviour, as assessed for general health and depressive/anxiety symptoms using Hamilton’s depression rating scale (HDRS), State and Trait Anxiety Inventory (STAI), Short Form 12 (SF 12).(T0 is the time of first treatment session.)
研究者
Dr Deepak S Ghadigaonkar
National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru