Clinical trial NCT05249309: Naturalistic Study of Ketamine in the Treatment of Depression
Official title: Naturalistic Study of Ketamine in the Treatment of Depression: Suicide Risk Assessment and Serum Measurements of SIRT3, suPAR, hsCRP, Interleukin 6, Complete Blood Count, Leptin, Lipid Profile and Blood Glucose
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Major Depressive Disorder
Bipolar Disorder
Bipolar Depression
Bipolar I Disorder
Bipolar II Disorder
Affective Disorder
Keywords: Ketamine
Suicide
Depression
Major depressive disorder
Major depression
Unipolar depression
Depressive disorders
Bipolar I disorder
Bipolar II disorder
Bipolar depression
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Federal University of Rio Grande do Sul
name: Hospital Moinhos de Vento
First posted: 2022-02-21
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Forty-five patients who fulfill the DSM-5 criteria for either MDD, Bipolar I disorder, or Bipolar II disorder who are currently in depressive episodes according to the structured clinical interview of the MINI. All participants must have been referred to receive ketamine for the treatment of a depressive episode at the Hospital de Clinicas de Porto Alegre (HCPA) and Hospital Moinhos de Vento (HMV).

Forty-fiver participants without any personal or first-degree family history of psychiatry or neurologic disorders will be recruited to participate as controls. Biochemical analyses will be used to investigate inflammatory markers, transcription factors and other peripheral biomarkers in patients with mood disorders and healthy controls

Brief summary: This study aims to examine the effect of ketamine in decreasing the risk of suicide in patients with depression and its effectiveness as an antidepressant agent.

Detailed description: Mood disorders are chronic, recurrent, and highly prevalent health conditions worldwide. Major depression and bipolar disorder are often associated with psychosocial functional impairments and general medical conditions. Furthermore, suicide figures as one of the most important negative outcomes of mood disorders. In this sense, according to the World Health Organization (WHO), psychiatric disorders are associated with more than 90% of cases of complete suicide and are responsible for 30% of reported suicide cases worldwide. Suicide is a matter of concern for clinicians, not only because of the individual and familiar impact but also due to its social and population impact; then, research involving new potential treatments for suicide behavior ate highly needed.

The literature has shown that ketamine, a substance commonly used as an anesthetic, is effective in treating depressive symptoms. Considering the high rate of suicide among patients with mood disorders and its consequences, the aim of this naturalistic study is to investigate the effect of ketamine in reducing the risk of suicide in patients with a depressive episode. The hypothesis is that treatment with ketamine will result in an improvement in depressive symptoms as well as in a decrease in the risk of suicide.

Therefore, forty-five patients will be recruited, with major depressive disorder, bipolar I disorder or bipolar II disorder and who were already on ketamine treatment prescribed by assistant psychiatrist (inclusion criteria). Patients will go on the standard protocol of ketamine 0.5mg/kg subcutaneously (SC) twice a week for one month in general. In line with a naturalistic approach, all changes in the protocol, in time and doses will be accepted, according to the assistant doctor prescription without study intervention.

After this period, they could receive the same dose of the medication once a week for the third month. In addition, patients will be monitored by phone until month six.

Forty-five participants without any personal or first-degree family history of psychiatry or neurologic disorders will be recruited to participate as controls. Biochemical analyses will be used to investigate inflammatory markers, transcription factors and other peripheral biomarkers in patients with mood disorders and healthy controls.

Eligibility criteria: Inclusion criteria

Having a diagnosis according to DSM-5 for

* Major depressive episode as part of either Major depressive disorder, Bipolar I disorder, or Bipolar II disorder according to Fifth Edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5);
* 18 years old or older;
* Be able to provide written informed consent.episode;
* MADRS scale total score ≥ 12 and score in items 1 (apparent sadness) and 2 (expressed sadness) ≥ 2 during the screening period (baseline);
* YMRS scale total score ≤ 11 at baseline;
* Having current symptoms of suicidal ideation and/or behavior, according to the C-SSRS scores;
* Use of effective contraceptive methods in the case of heterosexual women of childbearing age;
* Indication/prescription of the attending physician for the use of ketamine, subcutaneous;
* For the patients with Bipolar I disorder: currently using lithium, valproic acid, or atypical antipsychotic at therapeutic doses for at least four weeks prior to initial evaluation.
* For patients with Bipolar II disorder: currently using lithium, valproic acid, lamotrigine, or atypical antipsychotic at therapeutic doses for at least four weeks prior to initial evaluation.

Exclusion Criteria

* Patients with an unstable, defined, or suspected systemic medical condition;
* Women who are pregnant, breastfeeding or planning to become pregnant within the next year;
* Patients who cannot tolerate the use of ketamine or who have previous adverse effects associated with ketamine;
* Inability to comply with informed consent or treatment protocol needs;
* Patients currently with psychotic symptoms (according to DSM-5 criteria);
* Patients with a current diagnosis of any active substance use disorder according to the MINI/DSM-5 criteria (with the exception of tobacco);
* Patients with autoimmune or inflammatory conditions, cancer or active infectious diseases.

Primary outcomes:
measure: Changes in Columbia Suicide Severity Rating Scale (C-SSRS) - Ideation Severity
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Changes in Columbia Suicide Severity Rating Scale (C-SSRS) - Behavior
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
Secondary outcomes:
measure: Change in depressive symptoms according to Hamilton Depression Rating Scale (HAMD)
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Change in psychotic symptoms according to Brief Psychiatric Rating Scale (BPRS)
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Change in depressive symptoms according to Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Change in remission of manic symptoms according to Young Mania Rating Scale (YMRS)
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Change in functioning according to Functioning Assessment Short Test (FAST)
timeFrame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24
measure: Change in SIRT3 levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in suPAR levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in hsCRP levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in IL-6 levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in leptin levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in blood count.
timeFrame: For Weeks 1 and 4
measure: Change in lipid profile levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in blood glucose levels.
timeFrame: For Weeks 1 and 4
measure: Change in body weight
timeFrame: For Weeks 1 and 4
measure: Body height measurement
timeFrame: For Weeks 1 and 4
measure: Change in the Body Mass Index (BMI)
timeFrame: For Weeks 1 and 4
measure: Change in waist circumference
timeFrame: For Weeks 1 and 4
measure: Change in blood pressure
timeFrame: For Weeks 1, 2, 3 and 4
measure: Change in IL-10 levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in TNFalpha levels in the blood.
timeFrame: For Weeks 1 and 4
measure: Change in the Dietary Inflammatory Index (DII)
timeFrame: For Weeks 1 and 4
measure: Changes in proteomic markers
timeFrame: For Weeks 1 and 4
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
Study officials:
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Ana P Anzolin, Master
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Keila Maria M Ceresér, PhD
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Jéferson F Goularte, PhD
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Jairo Vinícius Pinto, MD, PhD
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Paulo B de Abreu, MD, PhD
role: STUDY_DIRECTOR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Ives C Passos, MD, PhD
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Márcia K Sant'Anna, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
name: Ellen Scotton, Master
role: STUDY_CHAIR
affiliation: Hospital Moinhos de Vento
name: Luciane N Cruz, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Cordova VHS, Anzolin AP, Sant'Ana MK, Lacerda A, Belmonte-de-Abreu PS. Allergic reaction induced by subcutaneous administration of ketamine: a case report. Int Clin Psychopharmacol. 2022 Sep 1;37(5):229-230. doi: 10.1097/YIC.0000000000000411. Epub 2022 May 2.