Clinical trial NCT04581603: CBT-I Augmentation of Medication for Drinking in AUD
Official title: Cognitive Behavioral Therapy (CBT-I) Augmentation of Topiramate in Promoting Abstinence in Alcohol Use Disorder (AUD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Alcohol Use Disorder With Insomnia
Keywords: Alcoholism
Sleep Initiation and Maintenance Disorders
Cognitive Behavioral Therapy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Coatesville Veterans Affairs Medical Center
First posted: 2020-10-09
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, behavioral placebo-controlled trial.
Primary purpose: TREATMENT

Brief summary: Alcohol Use Disorder (AUD) and insomnia are more prevalent in Veterans than in the general community. Furthermore, insomnia is comorbid in 36-91% of individuals with AUD and jeopardizes recovery by increasing their risk for relapse and complicating their clinical profile. The VA/DoD guidelines recommend four medications for the treatment of AUD by promoting abstinence and a reduction in drinking. Two of these medications (MED) used commonly are naltrexone and topiramate but they do not improve sleep continuity or insomnia. The recommended treatment for insomnia is Cognitive Behavioral Therapy for Insomnia (CBT-I), and it has shown efficacy in improving insomnia but with minimal benefit in improving abstinence. However, these studies have involved subjects in early or sustained remission. The proposed study will evaluate whether augmenting MED with CBT-I, after reducing drinking or achieving abstinence, bolsters recovery in AUD, by decreasing insomnia and improving abstinence. If this strategy shows good clinical results and the findings are replicated in a multi-center trial then the combination of MED with CBT-I should be considered a standard component of the initial management of AUD with insomnia.

Detailed description: Alcohol Use Disorder (AUD) and insomnia are both more prevalent among Veterans than in the general population. While insomnia is 3-9 times more prevalent in AUD than in the general population, patients with comorbid AUD and insomnia suffer from higher severity of AUD with increased alcohol craving, reduced quality of life, impaired interpersonal functioning, higher risks for suicidal behavior and relapse during early abstinence. There are limited options to treat drinking behavior and insomnia due to side effect profile (disulfiram). Medications commonly used to treat pathological drinking and promote abstinence include Naltrexone and Topiramate. However, these medications do not improve insomnia. Furthermore, hypnotic medication treatments with trazodone, gabapentin, and ramelteon have shown variable impact for sleep disturbance and abstinence. By contrast, all four studies evaluating Cognitive Behavioral Therapy for Insomnia (CBT-I) have shown a large magnitude of effect for treating insomnia but with minimal to no effect on abstinence. Thus, combining MED and CBT-I will improve their insomnia and bolster their recovery. This combination treatment will be the first personalized intervention in treating Veterans with AUD and comorbid insomnia.

A sample of treatment-seeking Veterans with AUD (N=82) will be initially treated with a medication for drinking (MED), that will be either TOP 200 mg a day for six weeks, naltrexone 50 mg daily (and up to 100 mg daily), depot-naltrexone 380 mg injections every 4 weeks, or a combination of TOP + NTX. They will stabilized on the MED over 6 weeks and then randomized to receive either CBT-I (N=41) or Sleep Hygiene Education (SHE, a behavioral placebo intervention) (N=41) weekly for the next eight weeks. The investigators will conduct CBT-I following the standard protocol using 30-minute sessions to deliver its components (Sleep Restriction, Stimulus Control, Sleep Hygiene and Cognitive Therapy). A post-intervention visit will be conducted eight weeks after the end of the intervention phase. The primary outcome measure will be the the insomnia severity (as assessed using the Insomnia Severity Index). The secondary outcome measure will include the Percent Days Abstinent (as computed from the Time Line Follow Back interview). The investigators will also track other aspects of alcohol use, sleep and daily functioning using TLFB, PACS, sleep diaries, BDI, and the STAI to test whether successful treatment of drinking and insomnia will be associated with better clinical outcomes in AUD. It is hypothesized that in Veterans with AUD, the combination of MED+CBT-I, as compared to MED+SHE group, will lead to superior sleep-related outcomes along with pre-post treatment effect sizes comparable to the meta-analytic norms. On an exploratory basis, the MED + CBT-I arm will have a relatively higher percentage of days abstinent from alcohol and the improvement in insomnia and abstinence from drinking will show durability eight weeks after end of behavioral sleep treatment. If these hypotheses are supported, the findings will need to be validated in a larger multi-center trial. If validated, the findings would support: 1) including insomnia treatment as a standard component of the initial protocol for treating AUD comorbid with insomnia, and 2) using MED+CBT-I combination treatment to manage this subpopulation of AUD patients.

Eligibility criteria: Inclusion Criteria:

* Male and female Veterans between the ages of 18 and 70 years.
* A past-year DSM-5 diagnosis of moderate to severe AUD (i.e., meeting 4 of the 11 DSM-5 criteria for AUD)
* Actively drinking alcohol within the past month ( 2 heavy drinking days, defined as 4 drinks/day for women and 5 drinks/day for men).
* Self-reported insomnia of moderate or severe intensity (i.e., an Insomnia Severity Index total score 15).
* Subject has expressed a desire to stop or reduce drinking.
* Capacity to comprehend and give informed consent.
* Women of child-bearing potential (i.e., who have not had a hysterectomy, bilateral oophorectomy, tubal ligation or is less than two years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative urine pregnancy test prior to initiation of treatment.

Exclusion Criteria:

General

* A current, clinically significant physical disease or abnormality based on history, physical examination, or routine laboratory evaluation.
* Current serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, eating disorder, or imminent suicide or violence risk).
* DSM-5 criteria for any other substance use disorder other than alcohol, nicotine, cannabis use disorder, or mild stimulant (cocaine) use disorder.
* Untreated subjects with a diagnosis of moderate-severe obstructive sleep apnea with a total Apnea Hypopnea Index (AHI-T) of 15 events/hour of sleep.
* Recent (within the 10 days prior to the baseline visit) exposure to licit or illicit opioids as defined by self-report or a positive urine drug screen. Individuals on a prescription low-dose opioid medication for chronic pain are eligible for treatment with TOP only, and positive urine drug screen(s) will not be exclusionary in this case.
* Patient also agrees not to initiate CBT for alcohol use disorder during the trial or will be discontinued.
* Completed a full course of CBT-I within the past year.

Specific to Naltrexone treatment

* A history of hypersensitivity to naltrexone.
* A transaminase elevation \>300% of normal.
* Active treatment with opioid medications.

Specific to Topiramate treatment

* A history of hypersensitivity to TOP.
* A history of nephrolithiasis.
* A history of narrow angle glaucoma.
* Current treatment with medications considered a high risk for adverse reactions for TOP treatment, such as carbonic anhydrase inhibitors.

Primary outcomes:
measure: Change in Insomnia Severity Index - Total Score
timeFrame: After eight weeks of behavioral sleep intervention
Secondary outcomes:
measure: Change in Percent Days Abstinent (PDA) on the Time Line Follow Back Measure
timeFrame: After eight weeks of behavioral sleep treatment
measure: Change in Percent Days Abstinent (PDA) on the Time Line Follow Back Measure
timeFrame: Eight weeks after end of behavioral sleep intervention (about 17 weeks since start of behavioral sleep treatment)
measure: Change in Insomnia Severity Index - Total Score
timeFrame: Eight weeks after end of behavioral sleep intervention (about 17 weeks since start of behavioral sleep treatment)
Other outcomes:
Locations:
city: Coatesville
country: United States
facility: Coatesville VA Medical Center, Coatesville, PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
state: Pennsylvania
Study officials:
affiliation: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
name: Subhajit Chakravorty, MD
role: PRINCIPAL_INVESTIGATOR
References: