Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression

NCT02360280 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CLNA-018-14S
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

About one-third of depressed patients will not get better after multiple antidepressant treatments. This situation put a high burden on patients with depression due to worsening quality of life and increasing health care costs. Difficult-to-treat depression might be even worse among Veterans given that the frequency of depressive symptoms is 2 to 5 times higher than among the general US population. A breakthrough discovery happened in recent years when investigators found that one infusion from an old anesthetic named ketamine showed high efficacy and rapid antidepressant effect (sometimes within hours) but lasted only up to a week. The investigators propose to study if multiple infusions of ketamine can provide greater and longer antidepressant effects than one infusion. If that is the case, multiple infusions could be an alternative to relieve depressive symptoms that do not response to multiple antidepressant drugs.

Conditions

Treatment-resistant Depression

Keywords

Depressive Disorder, Treatment-Resistant

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score After 12 Days of Treatment

  Average difference in the Montgomery-Asberg Depression Rating Scale (MADRS) score change between groups. The MADRS has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).

  13 days

Secondary Outcomes (3)

• Antidepressant Response Defined as >50% Decrease in MADRS Baseline Score

  13 days

• Remission Defined as MADRS Score Equal or Less Than 9

  13 days

• Time From Post-infusion Response to Occurrence of Relapse Defined as <50% of Baseline MADRS Score

  6 months

Study Arms (2)

Six ketamine infusions

EXPERIMENTAL

Six infusions of 0.5 mg/Kg of ketamine hydrochloride solution over 2 weeks.

Drug: ketamine

Single ketamine infusion preceded by 5 midazolam infusions

ACTIVE COMPARATOR

Single infusion of 0.5 mg/Kg of ketamine hydrochloride solution preceded by midazolam 0.045 mg/kg over 2 weeks.

Drug: ketamine; Drug: midazolam

Interventions

ketamine DRUG

sedative

Single ketamine infusion preceded by 5 midazolam infusions; Six ketamine infusions

midazolam DRUG

sedative

Single ketamine infusion preceded by 5 midazolam infusions

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Veterans aged 18 to 75 years.
• Have a telephone in their home and able to hear telephone conversations.
• Must meet current DSM-IV criteria for major depressive disorder (MDD), single or recurrent, without psychotic features confirmed by depression subset of the Structured Clinical Interview-Clinical Trial for DSM-IV (SCID).
• Have score 32 on the Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30)for severity of major depressive episode (MDE) at screening.
• Current major depressive episode resistant to treatment defined as failure to achieve improvement from at least 2 antidepressant trials of different pharmacological classes. Systematic evaluation of previous antidepressant trials will be assessed by the Antidepressant Treatment History Form (ATHF) .
• If applicable, current antidepressant dosages including augmenting agents and/or frequency and duration of psychotherapy sessions must remain stable for at least 6 weeks prior to beginning of the study.

You may not qualify if:

• Inability to speak English.
• Inability or unwillingness to provide written informed consent.
• Moderate/severe cognitive impairment by Mini Mental State Examination (MMSE) scores 27.
• Current or lifetime DSM-V criteria for post-traumatic stress disorder (PTSD), acute stress disorder, psychosis-related disorder, bipolar disorder I or II disorder, substance-induced mood disorder, any mood disorder due to a general medical condition or any Axis I disorder other than MDD as the primary presenting problem.
• History of moderate or severe traumatic brain injury, Parkinson's disease, dementia of any type, multiple sclerosis, seizures or other central nervous system (CNS) related disorders.
• History of comorbid substance disorder within 6 months of assessment plus positive urine toxicology screen test during baseline assessments.
• Clinically unstable medical illness that could compromise the patient's ability to tolerate or likely interfere with the study procedures (e.g., history of or current myocardial ischemia or arrhythmias, congestive heart failure, severe pulmonary, renal, or hepatic disease, uncontrolled hypertension).
• Current or within less than 14 days use of barbiturates or monoamine oxidase inhibitors (MAOi).
• For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study.
• Imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Mayo Clinic: collaborator
• University of Minnesota: collaborator

Study Sites (1)

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

Location

Related Publications (2)

• Shiroma PR, Thuras P, Wels J, Albott CS, Erbes C, Tye S, Lim KO. Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2020 Dec 1;277:470-477. doi: 10.1016/j.jad.2020.08.058. Epub 2020 Aug 26.

  PMID: 32871534 RESULT

• Shiroma PR, Thuras P, Wels J, Albott CS, Erbes C, Tye S, Lim KO. A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression. Transl Psychiatry. 2020 Jun 26;10(1):206. doi: 10.1038/s41398-020-00897-0.

  PMID: 32591498 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Paulo R. Shiroma
• Organization: Minneapolis VA Medical Center

paulo.shiroma@va.gov

612-467-2264

Study Officials

• Paulo R Shiroma, MD

  Minneapolis VA Health Care System, Minneapolis, MN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 10, 2015
• Study Start: April 1, 2015
• Primary Completion: October 22, 2018
• Study Completion: March 19, 2019
• Last Updated: April 25, 2024
• Results First Posted: December 3, 2019

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)