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Trial record 5 of 101 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Texas, United States ) | NIH, U.S. Fed

Ketamine for Treatment Resistant Late-Life Depression

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ClinicalTrials.gov Identifier: NCT02556606
Recruitment Status : Recruiting
First Posted : September 22, 2015
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal and lasts the longest, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depressive Disorder Drug: Ketamine Drug: Midazolam Phase 3

Detailed Description:

Primary Aim: To identify and evaluate the durability of benefit of the best performing of 3 sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (MID) (0.03 mg/kg) infusion in up to 72 Veterans with Late-Life Treatment Resistant Depression (LL-TRD).

Hypothesis 1: the durability of benefit of a single KET 0.5 mg/kg infusion is superior to (0.1 mg/kg, 0.25 mg/kg, and MID 0.03 mg/kg) time to relapse as measured by repeated measurements using the Montgomery-Asberg Depression Rating Scale (MADRS) during a four-week, post-infusion follow-up.

Secondary Aim: To evaluate and compare the antidepressant efficacy of the best performing of 3 sub-anesthetic doses of a single KET (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and MID (0.03 mg/kg) infusion in vets with LL-TRD, using a triple blind (patient, rater, anesthesiologist) Bayesian adaptive randomization design.

Hypothesis 2: a single KET 0.5 mg/kg infusion will be superior to a single infusion of KET (0.1 mg/kg), KET (0.25 mg/kg), and MID 0.03 mg/kg) as measured by the proportion of participants demonstrating > 50% reduction on MADRS scores at 72-hour post-infusion.

Tertiary Aim: To evaluate the immediate and longer-term safety and tolerability of the most effective KET infusion (0.5 mg/kg) relative to MID (0.03 mg/kg) in vets with LL-TRD.

Hypothesis 3: KET infusion at the most effective dose (0.5 mg/kg) will be safe and well tolerated compared to MID, as assessed by psychoactive and general side effect rating scales during and up to 4 weeks post study infusion.

Exploratory Aims:

  1. To measure the effects of the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on neurocognitive performance.
  2. To measure the effects the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on peripheral biomarkers of cellular plasticity and inflammation.
  3. To measure the effects the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on resting-state quantitative electroencephalography.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine for Treatment Resistant Late-Life Depression
Actual Study Start Date : October 1, 2015
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketamine 0.10 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg
Drug: Ketamine
randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg

Experimental: Ketamine 0.25 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg
Drug: Ketamine
randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg

Experimental: Ketamine 0.50 mg/kg
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg
Drug: Ketamine
randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg

Active Comparator: Midazolam 0.03 mg/kg
randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg
Drug: Midazolam
single 40 min infusion of MID 0.03mg/Kg




Primary Outcome Measures :
  1. time to relapse [ Time Frame: four-week, post-infusion follow-up ]
    the durability of benefit of a single KET 0.5 mg/kg infusion is superior to (0.1 mg/kg, 0.25 mg/kg, and MID 0.03 mg/kg) time to relapse as measured by repeated measurements using the Montgomery-Asberg Depression Rating Scale during a four-week, post-infusion follow-up.


Secondary Outcome Measures :
  1. proportion of participants demonstrating > 50% reduction on Montgomery-Asberg Depression Rating Scale scores [ Time Frame: at 72-hour post-infusion ]
    To evaluate and compare the antidepressant efficacy of the best performing of three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) infusion in Veterans with LL-TRD, using a triple blind (patient, rater, anesthesiologist) Bayesian adaptive randomization design to determine if a single KET 0.5 mg/kg infusion will be superior to a single infusion of KET (0.1 mg/kg), KET (0.25 mg/kg), and MID 0.03 mg/kg) as measured by the proportion of participants demonstrating > 50% reduction on Montgomery-Asberg Depression Rating Scale scores at 72-hour post-infusion.


Other Outcome Measures:
  1. psychoactive side effect rating scales [ Time Frame: during and up to four week post study infusion ]
    To evaluate the immediate and longer-term safety and tolerability of the most effective KET infusion (0.5 mg/kg) relative to midazolam (0.03 mg/kg) by assessing psychoactive side effect rating scales using the Clinician-Administered Dissociative States Scale (CADSS) during and up to four week post study infusion.

  2. performance on neurocognitive assessments [ Time Frame: Screening phase through four weeks post study infusion ]
    To measure the effects of the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on neurocognitive performance assessed with the MATRICS Consensus Cognitive Battery (MCCB) and MMSE assessment tools.

  3. peripheral biomarkers of cellular plasticity [ Time Frame: day of the infusion at baseline, 120 minutes, 240 minutes, 8 hours, and 7 days post infusion and four weeks post infusion ]
    To measure the effects the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on peripheral biomarkers of cellular plasticity by brain-derived neurotrophic factor (BDNF) measures from blood samples taken.

  4. resting-state quantitative electroencephalography [ Time Frame: pre-infusion, 28 and 60 minutes after start of infusion, 2 and 3 hours after end of infusion and 1, 3, and 7 days after ketamine infusion. ]
    To measure the effects the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on resting-state quantitative electroencephalography. Pharmaco-EEG (12 minutes of alternating 1-minute eyes open and closed) will be assessed pre-infusion, 28 minutes after start of infusion, 60 minutes after start of infusion, and 2 and 3 hours after end of infusion and 1, 3, and 7 days after ketamine infusion.

  5. general side effect rating scales [ Time Frame: during and up to four weeks post study infusion ]
    To evaluate the immediate and longer-term safety and tolerability of the most effective KET infusion (0.5 mg/kg) relative to midazolam (0.03 mg/kg) by assessing general side effect rating scales using the PRISE assessment tool during and up to four week post study infusion.

  6. peripheral biomarkers inflammation [ Time Frame: day of the infusion at baseline, 120 minutes, 240 minutes, 8 hours, and 7 days post infusion and four weeks post infusion ]
    To measure the effects the most effective dose of KET (0.50 mg/kg) relative to MID (0.03 mg/kg) on peripheral biomarkers of inflammation by measuring Interleukin from blood sample taken.



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients, 55 years of age,
  • Participants must fulfill DSM 5 criteria for a Major Depressive Episode (Unipolar), based on a structured diagnostic interview, the DSM 5 M.I.N.I. 7.0
  • Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration),
  • Participants have not responded to two or more adequate trials of FDA-approved antidepressants, determined by Antidepressant Treatment Response Questionnaire (ATRQ) criteria.
  • Participants must score 14 or greater on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), and score 27 on the Montgomery Asberg Depression Rating Scale (MADRS),
  • Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.

Exclusion Criteria:

  • Patients currently on fluoxetine,
  • History of schizophrenia, schizoaffective disorder or any psychotic disorder, or bipolar disorder,
  • Documented history of a psychotic disorder in a first-degree relative,
  • Current diagnosis of obsessive-compulsive disorder (OCD) or eating disorder [bulimia nervosa or anorexia nervosa],
  • Alcohol or substance use [except nicotine] within the preceding 6 months,
  • Patients with any clinically significant personality disorder that would, in the investigator's judgment, preclude safe study participation,
  • Patients judged to be at serious and imminent suicidal or homicidal risk,
  • Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury],
  • For study entry, patients must be reasonable medical candidates for ketamine or midazolam infusion, as determined by a board-certified physician co-investigator during study Screening,
  • Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG,
  • Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg),
  • Patients with one or more 11 seizures without a clear and resolved etiology,
  • Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening,
  • Past intolerance or hypersensitivity to ketamine, or history of recreational use of phencyclidine (PCP) or ketamine,
  • Past intolerance or hypersensitivity to midazolam,
  • Age-related cognitive decline or mild dementia suggested by a score of < 25 on the Mini-Mental State Examination (MMSE) at Screening,
  • Patients taking medications with known activity at the N-methyl-D-aspartate receptor (NMDA) or AMPA glutamate receptor [e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine], or the muopioid receptor,
  • Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide,
  • Patients who demonstrate > 25% decrease in depressive symptoms as reflected by the QIDS-SR score from Screening to Randomization,
  • Patients who have received electroconvulsive therapy (ECT) in the past 6 months prior to Screening,
  • Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556606


Contacts
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Contact: Sanjay Mathew, MD (713) 791-1414 ext 24159 Sanjay.Mathew@va.gov
Contact: Tabish Iqbal (713) 798-1075 tiqbal@bcm.edu

Locations
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United States, Texas
Michael E. DeBakey VA Medical Center, Houston, TX Recruiting
Houston, Texas, United States, 77030
Contact: Sanjay Mathew, MD    713-791-1414 ext 24159    Sanjay.Mathew@va.gov   
Contact: Tabish Iqbal    (713) 798-1075    tiqbal@bcm.edu   
Sub-Investigator: Rayan K. Al-Jurdi, MD         
Principal Investigator: Sanjay Mathew, MD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Sanjay Mathew, MD Michael E. DeBakey VA Medical Center, Houston, TX

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02556606     History of Changes
Other Study ID Numbers: CLNA-001-14F
First Posted: September 22, 2015    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
ketamine
depression
treatment resistant
treatment resistant depression
late life depression
depression in the elderly
geriatric depression

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents