Zonisamide as a New Treatment for Post-Traumatic Stress Disorder and Co-Occurring Alcohol Use Disorder
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity score
研究概览
简要总结
The objective of this study is to determine if, compared to placebo, zonisamide (400mg/day) is a safe and efficacious treatment for post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) in Veterans with PTSD and co-occurring AUD.
详细描述
This is a randomized, double-blind, placebo-controlled study to examine the ability of 5-weeks treatment with zonisamide to reduce symptoms of PTSD and AUD. The study population will consist of 60 Veterans with combat-related PTSD and co-morbid AUD. Veterans will be randomized 1:1 to receive either zonisamide (up to 400 mg/day) or placebo daily for 35±4days, followed by a 14-day down-titration period with follow-up. Primary efficacy variables are scores on the CAPS-5, fear-potentiated startle (FPS) responses, and percent of heavy drinking days (%HDD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study will be conducted in a double-masked fashion in that both the participants and the site investigators and staff interacting with participants and assessing study outcomes will be masked to treatment assignment. The only individuals at the site with assess to treatment assignment information will be the research pharmacists.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be willing and able to sign and date an informed consent form
- •Be a military service member or Veteran
- •Male or female, 18-55 years of age
- •Meet Diagnostic and Statistical Manual (DSM)-5 criteria for AUD
- •Meet the DSM-5 diagnostic criteria for PTSD; PTSD diagnosis and severity will be determined based on CAPS-5 score greater than or equal to 33
- •Self-report drinking heavily (5 standard units for males, 4 for females) on at least 30% of the 42 days prior to the screening interview
- •Score less than 10 on the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) assessed in the context of a breath alcohol concentration (BAC) less than or equal to 0.02% to demonstrate that they do not need medical detoxification (Sullivan et al. 1989)
- •Have blood lab tests assessed at screening with ranges falling within the acceptable limits as noted in the protocol.
- •Have normal vitals (heart rate 60-100 bpm, systolic blood pressure 90-140 mmHg and diastolic blood pressure 60-90 mmHg) and a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, normal QTc, and no clinically significant arrhythmias. Note that clinical judgement will be used when characterizing bradycardia among some healthy subject populations, for example, conditioned veterans. Thus, some individuals with bradycardia (i.e., heart rate less than 60 bpm) may be enrolled as determined by the admitting physician.
- •Have a self-reported medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician
- •Psychotropic medication free (with exception of SSRIs/SNRIs) for 7 or more days (or longer, depending on medication half-life) prior to enrollment
- •Be willing/able to stop use of any sleep medication for the duration of the study
- •Be willing to comply with all study procedures and be available for the duration of the study
- •Women must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or using double-mode form of contraception (i.e. barrier plus, e.g., birth control pills + intrauterine device, condoms + spermicide, etc.). Women can be receiving hormone replacement treatment (HRT) if the HRT dose has been stable for a period of at least 3 months
- •Women must provide negative urine pregnancy tests prior to randomization
- •Be willing to undergo a hearing test and be able to detect 500-2000 Hz tones at 40 dB or less.
排除标准
- •DSM-5 criteria for substance use disorders other than alcohol or nicotine or test positive for prescription or illegal drugs. Regarding marijuana/THC, an individual must test negative at the screening. If an individual's test is positive, they will be given a grace period where they will have the opportunity to return and test negative prior to being enrolled.
- •Be pregnant or nursing
- •Be taking blood pressure medications, psychotropics (with exception of SSRIs/SNRIs), drugs effecting the CNS, medications contraindicated with ethanol, any sulfonamide, or any other medication that could interact with study medications or alter the effects of alcohol.
- •a. Note that participants may currently be seeking treatment (or already receiving a behavioral treatment) for AUD, but may not be taking medications used in the treatment of AUD (acamprosate, disulfiram, oral naltrexone, and extended-release injectable naltrexone, and topiramate)
- •Have neurological or psychiatric disorders other than PTSD or AUD (except mild/moderate depression succeeding PTSD). Examples include:
- •Current psychosis, bipolar illness or major depression requiring treatment.
- •Organic brain disease or dementia assessed clinical interview.
- •History of any psychiatric disorder which would require ongoing treatment or which would make study compliance difficult.
- •History of suicide attempts within the past year and/or current suicidal ideation/plan
- •Have evidence of untreated or unstable medical illness including: cardiovascular, neuroendocrine, autoimmune, renal, hepatic, or active HIV+, AIDS infection.
- •Have a history of medically adverse reactions to alcohol (e.g., loss of consciousness, chest pain, or epileptic seizure) or major alcohol-related medical complications requiring hospitalization (i.e. hepatitis or pancreatitis)
- •Have contraindication(s) to take the study medications such as renal or hepatic impairment, congenital metabolic disorders, or hypersensitivity/allergies to study drug or similar compounds
- •Have current epilepsy or evidence suggestive of seizure disorder
- •Have past brain injury/head trauma with current symptoms (e.g. not photophobic, dizziness, etc.) or past report of loss of consciousness (LOC) for greater than 30 minutes and/or have been blast-exposed or had LOC of greater than 1 minute and current post-concussive symptoms
- •Self-report more than thirty days abstinence from alcohol during the three months prior to enrollment/consent
- •Current signs of violence or aggression, assessed as part of the consent process
- •Participation in a pharmaceutical trial or exposure to any investigational drugs within 1 month of the screening visit
- •Hearing loss that would interfere with the FPS measures
- •Have any other illness, condition, or use medications (psychotropic or antiretroviral), which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study
研究组 & 干预措施
Zonisamide (up to 400 mg/day)
Zonisamide capsules titrated to a maximum tolerated dose of 400 mg/day for 35 days +/- 4 days, followed by a 14 day down-titration period.
干预措施: Zonisamide (Drug)
Placebo
Encapsulated placebo filler (lactose) for 35 +/- 4 days, followed by a 14 day down-titration period. Placebo will go through a similar perceived titration process to maintain blind.
干预措施: Placebo Comparator (Drug)
结局指标
主要结局
Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity score
时间窗: Baseline to post-treatment (weeks 0, 3, 5, 7)
CAPS-5 is a 30-item questionnaire, corresponding to the DSM-5 diagnosis for PTSD. All symptoms are assessed on a five-point scale (0=Absent, 1=Mild/subthreshold, 2=Moderate/threshold, 3=Severe/markedly elevated, 4=Extreme/incapacitating). CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms, possible scores ranging from 0-80 with higher values indicating a worse symptom severity.
Percent change in fear-potentiated startle (FPS) responses from acquisition on day 1 to recall on day 35.
时间窗: Baseline to post-treatment (weeks 1, 5, 7)
Change from baseline in the percent of heavy drinking days (%HDD)
时间窗: Baseline to post-treatment (weeks 0-7)
Timeline Follow-Back (TLFB) of self-report assessment of heavy drinking days over the course of the five-week study treatment.
次要结局
- Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) subscale scores: Criterion C (Avoidance)(Baseline to post-treatment (Weeks 0, 3, 5, 7))
- Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) subscale scores: Criterion D (negative alterations in cognitions and mood)(Baseline to post-treatment (Weeks 0, 3, 5, 7))
- Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) subscale scores: Criterion E (hyperarousal)(Baseline to post-treatment (Weeks 0, 3, 5, 7))
- Severity and numbers of AEs(Baseline to post-treatment (weeks 0-7))
- Treatment retention(Baseline to post-treatment (weeks 0-5))
- Medication compliance(Baseline to post-treatment (weeks 0-5))
- Medication adherence(Baseline to post-treatment (weeks 0-5))
- Blood pressure(Baseline to post-treatment (weeks 0-7))
- Heart rate(Baseline to post-treatment (weeks 0-7))
- ECG abnormalities(Baseline to post-treatment (weeks 0-7))
- Breath alcohol content (BAC)(Baseline to post-treatment (weeks 0-7))
- Subjective and psychometric effects of alcohol (e.g. mood, urge/craving)(Baseline to post-treatment (weeks 0-7))
- Alcohol use measures(Baseline to post-treatment (weeks 1, 3, 7))
- Presence and symptom assessments for PTSD(Baseline to post-treatment (weeks 0-7))
- Change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) subscale scores: Criterion B (reexperiencing)(Baseline to post-treatment (Weeks 0, 3, 5, 7))