Anxiety During Abstinence in AUD

Официальное название

Neural Mechanisms of Anxiety During Early and Protracted Abstinence in Alcohol Use Disorder

Обзор

The goal of this study is to better understand the underlying neurobiological basis of anxiety that emerges during abstinence in patients with alcohol use disorder (AUD). The main questions it aims to answer are: 1. To characterize anxiety itself as well as anxiety related-neurobiological circuitry in early abstinence in AUD 2. To examine how anxiety and anxiety related-neurobiological circuitry change over the course of abstinence in AUD Researchers will recruit both participants with AUD and healthy volunteers. The participants with AUD will be prescribed disulfiram, a medication that helps participants with AUD stay abstinent. Healthy volunteers will not receive antabuse. Patients with AUD will undergo fMRI scanning both after 1 week and 3 months of disulfiram treatment. Healthy volunteers will undergo fMRI once.

Подробное описание

This study will recruit 40 treatment-seeking participants with AUD ("AUDP") and 20 age matched healthy volunteer participants (HVP). AUDP will be initiated on disulfiram, a medication FDA approved for alcohol use disorder that is a first line treatment for maintenance of abstinence from alcohol, to facilitate and help ensure abstinence from alcohol and will undergo functional MRI scanning at two timepoints: 1) 8-14 days after the last drink ("early abstinence") and 2) after three months of abstinence ("protracted abstinence"). HVP will be scanned once. The investigators will examine the functioning of the Anterior Insula (AI), Bed Nucleus of the Stria Terminalis (BNST), and Dorsolateral Prefrontal Cortex (DLPFC) during a task that evokes anxiety while anticipating an uncertain threat ("threat-anxiety") as well as resting state functional connectivity (RSFC) between AI-BNST and AI-DLPFC to measure whether there are neuroplastic changes in these circuits that occur during abstinence. These changes in anxiety circuit activity and connectivity will be related to changes in current anxiety symptoms.

Вмешательства

• Препарат Disulfiram 250 mg
  Disulfiram will be used in Participants with Alcohol Use Disorder only to facilitate abstinence.
• Диагностический тест functional MRI
  Participants will undergo fMRI scanning. Participants with alcohol use disorder will undergo scanning after 1 week and 3 months of disulfiram maintenance. Healthy volunteer participants will undergo scanning once.

Первичные конечные точки

• AI-BNST Resting state functional connectivity correlation (R) value [Срок оценки: 1 week and 3 months]
• AI-BNST task activation t statistic [Срок оценки: 1 week and 3 months]
• State trait anxiety inventory score [Срок оценки: 1 week and 3 months]

Критерии участия

Inclusion Criteria (Participants with Alcohol use Disorder):

• Between the ages of 21 and 55
• Right-handed
• Able to perform informed consent and comply with study
• Seeking treatment for AUD
• Meets The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for AUD of at least moderate severity (>3 symptoms)

Inclusion Criteria (Healthy Volunteer Participants):

• Between the ages of 21 and 55
• Right-handed
• Able to perform informed consent and comply with study
• Report drinking an average of fewer than 8/15 standard drinks per week for women/men and no more than 1 HDD (heavy drinking days) during the previous 28 days.

Exclusion Criteria (Participants with Alcohol use Disorder):

• Neurological, medical or other conditions that would interfere with MRI scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non MRI-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair-bound, tattoos as indicated by the guidelines established by the Zuckerman Institute MRI unit: https://mr.research.columbia.edu/
• DSM 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder
• Any non-AUD psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study
• Significant suicide or violence risk
• Currently taking psychotropic medication
• Current substance use disorder other than AUD, tobacco use disorder or mild cannabis use disorder
• Currently pregnant, attempting to become pregnant or nursing
• Sufficiently socially unstable as to preclude participation (e.g. homeless).
• Known history of allergy, intolerance, or hypersensitivity to disulfiram or its derivates
• Contraindications to disulfiram treatment (e.g. liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuram derivatives)
• Currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline.
• Treatment with concomitant medications that might interfere with disulfiram
• A history of alcohol withdrawal seizures, delirium tremens or resistant alcohol withdrawal
• Current moderate or severe alcohol withdrawal (CIWA >9 with BAL<0.05)
• History of prior disulfiram treatment failure
• Being abstinent for > 7 days at the time of screening

Exclusion Criteria (Healthy Volunteer Participants):

• Neurological, medical or other conditions that would interfere with MRI scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non MRI-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight>300 lbs., wheelchair- bound, tattoos as indicated by the guidelines established by the ZI MRI unit: https://mr.research.columbia.edu/
• DSM 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder
• Any psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study
• Significant suicide or violence risk
• Currently taking psychotropic medication
• Current substance use disorder other than tobacco use disorder or mild cannabis use disorder
• Currently pregnant, attempting to become pregnant or nursing
• Sufficiently socially unstable as to preclude participation (e.g., homeless).
• A diagnosis of AUD of any severity

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Columbia University Irving Medical Center — New York

Публикации

• Anker JJ, Kushner MG, Thuras P, Menk J, Unruh AS. Drinking to cope with negative emotions moderates alcohol use disorder treatment response in patients with co-occurring anxiety disorder. Drug Alcohol Depend. 2016 Feb 1;159:93-100. doi: 10.1016/j.drugalcdep.2015.11.031. Epub 2015 Dec 11. PMID 26718394
• Anker JJ, Kushner MG. Co-Occurring Alcohol Use Disorder and Anxiety: Bridging Psychiatric, Psychological, and Neurobiological Perspectives. Alcohol Res. 2019 Dec 30;40(1):arcr.v40.1.03. doi: 10.35946/arcr.v40.1.03. eCollection 2019. PMID 31886106
• Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, Ugurbil K, Andersson J, Beckmann CF, Jenkinson M, Smith SM, Van Essen DC. A multi-modal parcellation of human cerebral cortex. Nature. 2016 Aug 11;536(7615):171-178. doi: 10.1038/nature18933. Epub 2016 Jul 20. PMID 27437579
• Brown SA, Irwin M, Schuckit MA. Changes in anxiety among abstinent male alcoholics. J Stud Alcohol. 1991 Jan;52(1):55-61. doi: 10.15288/jsa.1991.52.55. PMID 1994124
• Centanni SW, Morris BD, Luchsinger JR, Bedse G, Fetterly TL, Patel S, Winder DG. Endocannabinoid control of the insular-bed nucleus of the stria terminalis circuit regulates negative affective behavior associated with alcohol abstinence. Neuropsychopharmacology. 2019 Feb;44(3):526-537. doi: 10.1038/s41386-018-0257-8. Epub 2018 Nov 2. PMID 30390064
• Clauss JA, Avery SN, Benningfield MM, Blackford JU. Social anxiety is associated with BNST response to unpredictability. Depress Anxiety. 2019 Aug;36(8):666-675. doi: 10.1002/da.22891. Epub 2019 Apr 6. PMID 30953446
• Agarwal R, Sharma SK, Malaviya AN. Gold-induced hypersensitivity pneumonitis in a patient with rheumatoid arthritis. Clin Exp Rheumatol. 1989 Jan-Feb;7(1):89-90. PMID 2706825
• Driessen M, Meier S, Hill A, Wetterling T, Lange W, Junghanns K. The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders. Alcohol Alcohol. 2001 May-Jun;36(3):249-55. doi: 10.1093/alcalc/36.3.249. PMID 11373263

Идентификаторы

NCT: NCT06793488 · AAAV4012 · K23AA030355

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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