Cannabidiol for Treatment Resistant Depression

NCT04732169 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 300006618
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

With this study, the investigators will address the following scientific aims:

1. 1.Demonstrate the antidepressant effects of CBD in human adults with treatment refractory MDD as measured by standard rating scales.
2. 2.Confirm CBD's safety profile in human adult patients with MDD.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (3)

• Hamilton Depression Rating Scale- 17

  A semi-structured interview focusing on 17 symptoms of depression, range of scores 0-52 with 0 indicating no depression

  Baseline

• Hamilton Depression Rating Scale- 17

  A semi-structured interview focusing on 17 symptoms of depressionrange of scores 0-52 with 0 indicating no depression,

  Week 8

• Hamilton Depression Rating Scale- 17

  A semi-structured interview focusing on 17 symptoms of depression, range of scores 0-52 with 0 indicating no depression.

  Week 16

Secondary Outcomes (3)

• Montgomery Asberg Depression Rating Scale

  Baseline

• Montgomery Asberg Depression Rating Scale

  Week 8

• Montgomery Asberg Depression Rating Scale

  Week 16

Study Arms (2)

Epidiolex (cannabidiol) (CBD)

ACTIVE COMPARATOR

During the first week after randomization, participants will receive 125mg of Epidiolex (CBD) or matching placebo taken twice daily (250mg/day). During the second week after randomization, the dosage will be increased to 250mg of Epidiolex or placebo taken twice daily (500mg/day) for one week. During the third week after randomization, the dosage will be increased to 500mg of Epidiolex (CBD) or matching placebo taken twice daily (1000mg/day). Participants will remain on 1000mg/day of Epidiolex (CBD) or matching placebo for four more weeks, at which point they will be stepped down to 500mg/day of Epidiolex (CBD) or placebo for one week, followed by 250mg/day of Epidiolex (CBD) or placebo for one week.

Drug: Active study drug ( oral CBD)

Placebo

PLACEBO COMPARATOR

During the first week after randomization, participants will receive 125mg of Epidiolex (CBD) or matching placebo taken twice daily (250mg/day). During the second week after randomization, the dosage will be increased to 250mg of Epidiolex or placebo taken twice daily (500mg/day) for one week. During the third week after randomization, the dosage will be increased to 500mg of Epidiolex (CBD) or matching placebo taken twice daily (1000mg/day). Participants will remain on 1000mg/day of Epidiolex (CBD) or matching placebo for four more weeks, at which point they will be stepped down to 500mg/day of Epidiolex (CBD) or placebo for one week, followed by 250mg/day of Epidiolex (CBD) or placebo for one week.

Drug: matching placebo

Interventions

Active study drug ( oral CBD) DRUG

CBD in single dose syringes

Epidiolex (cannabidiol) (CBD)

matching placebo DRUG

Placebo made with sesame oil flavored with strawberry flavoring in single dose syringes

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years old
• Sufficient fluency in English to understand testing procedures and provide written informed consent
• A Hamilton Depression Rating Scale total score greater than 18
• A DSM 5 diagnosis of MDD based on the MINI.
• No evidence of alcohol or other substance use disorder in the past 3 months
• For females: no current pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy test at screening).
• Depressed patients who have failed at least one adequate antidepressant trial during the current depressive episode based on the ATRQ.

You may not qualify if:

• No diagnosis of other primary psychiatric disorder (defined in this case as being the main focus of treatment) as determined by the MINI, such as: bipolar disorder, personality disorders, psychotic disorders, post-traumatic stress disorder, obsessive-compulsive disorder, dissociative disorders, eating disorder, or cognitive task due to neurological conditions
• Systolic blood pressure \< 150 and/or diastolic blood pressure \< 90 at screening
• A QTc F\< 480 as determined by an ECG
• No post-partum state (being within 2 months of delivery or miscarriage)
• Imminent suicide or homicide risk as determined by the investigator
• No history of using prescription Epidiolex for any indication.
• Not being treated with one of the following medications: benzodiazepines or other CNS depressants.
• Not using concomitant medications that are moderate or strong CYP3A4 or CYP2C19 inhibitors.
• None of the following clinically-significant medication condition or therapy that would preclude treatment with ketamine, to include: Recent myocardial infarction, unstable angina, malignant neoplasm in the past 6 months, immunosuppressive or corticosteroid therapy within the last month, with the following exceptions: any inhaled, intranasal, topical or vaginal corticosteroids are allowed, chemotherapy.
• No clinically significant neurological disease based on medical history (e.g., epilepsy) or significant head injury.
• Any of the following disorders: Rheumatoid arthritis; Lupus erythematosus; Autoimmune hepatitis; Autoimmune peripheral neuropathy; Autoimmune pancreatitis; Behcet's disease; Crohn's disease; Autoimmune glomerulonephritis; Grave's disease; Guillain-Barre syndrome; Hashimoto's thyroiditis; Autoimmune polymyositis or polymyalgia; Myasthenia gravis; Narcolepsy; Polyarteritis nodosa; Scleroderma; Sjogren's syndrome; Transverse myelitis; Wegener's granulomatosis; History of seizures (only childhood febrile seizures are allowed)
• The presence of clinically significant laboratory findings in the opinion of the investigator including, but not limited to, clinically significant anemia or transaminase elevation.
• If the UDS is positive, the subject would be excluded if, in the opinion of the investigator, the positive UDS meant the subject has an active substance use disorder.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (10)

• Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015 Feb;76(2):155-62. doi: 10.4088/JCP.14m09298.

  PMID: 25742202 BACKGROUND

• Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.

  PMID: 12813115 BACKGROUND

• Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231-42. doi: 10.1056/NEJMoa052963.

  PMID: 16554525 BACKGROUND

• Linge R, Jimenez-Sanchez L, Campa L, Pilar-Cuellar F, Vidal R, Pazos A, Adell A, Diaz A. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology. 2016 Apr;103:16-26. doi: 10.1016/j.neuropharm.2015.12.017. Epub 2015 Dec 19.

  PMID: 26711860 BACKGROUND

• Silote GP, Sartim A, Sales A, Eskelund A, Guimaraes FS, Wegener G, Joca S. Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms. J Chem Neuroanat. 2019 Jul;98:104-116. doi: 10.1016/j.jchemneu.2019.04.006. Epub 2019 Apr 27.

  PMID: 31039391 BACKGROUND

• Gall Z, Farkas S, Albert A, Ferencz E, Vancea S, Urkon M, Kolcsar M. Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression. Biomolecules. 2020 May 22;10(5):801. doi: 10.3390/biom10050801.

  PMID: 32455953 BACKGROUND

• Shbiro L, Hen-Shoval D, Hazut N, Rapps K, Dar S, Zalsman G, Mechoulam R, Weller A, Shoval G. Effects of cannabidiol in males and females in two different rat models of depression. Physiol Behav. 2019 Mar 15;201:59-63. doi: 10.1016/j.physbeh.2018.12.019. Epub 2018 Dec 17.

  PMID: 30571957 BACKGROUND

• Sales AJ, Fogaca MV, Sartim AG, Pereira VS, Wegener G, Guimaraes FS, Joca SRL. Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex. Mol Neurobiol. 2019 Feb;56(2):1070-1081. doi: 10.1007/s12035-018-1143-4. Epub 2018 Jun 4.

  PMID: 29869197 BACKGROUND

• Cuttler C, Spradlin A, McLaughlin RJ. A naturalistic examination of the perceived effects of cannabis on negative affect. J Affect Disord. 2018 Aug 1;235:198-205. doi: 10.1016/j.jad.2018.04.054. Epub 2018 Apr 6.

  PMID: 29656267 BACKGROUND

• McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15.

  PMID: 29241357 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Matthew Macaluso, D.O.

  University ot Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Bee McWane Reid Professor, Department of Psychiatry & Behavioral Neurobiology

Model Details: We plan to administer Epidiolex (CBD) or placebo in double blind, randomized, cross-over fashion.

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: February 1, 2021
• Study Start: July 1, 2021
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: July 19, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 3 years
• Access Criteria: Will share with public

Locations

US (1)