Trial record 16 of 16 for:    Batten Disease

Action of Ketamine in Treatment-Resistant Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Ottawa
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Pierre Blier, University of Ottawa
ClinicalTrials.gov Identifier:
NCT01945047
First received: May 22, 2013
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

Depression carries the largest burden of all medical disorders in middle to high income countries, as determined by the World Health Organization. Despite many antidepressant strategies, only a third of patients get well after their first treatment and a third remain ill after several treatments. Moreover, antidepressant treatments all have a delayed action ranging up to several weeks.

Ketamine (KET) has been used for decades as a sedative and anesthetic. In treatment-resistant depressed patients(TRD), an intravenous dose much lower than necessary for anesthesia may produce a robust antidepressant effect and may even abolish suicidal thoughts within hours, peaking within 24 hours. But, its antidepressant effect generally lasts only days.Previous studies examining KET in TRD have been critiqued for lack of an effective placebo measure due to brief perceptual experiences associated with KET. Thus, the current study compares KET against a short-acting sedative. The phases of this study compare response to a single KET injection to 6 injections over 2 weeks. Next, KET responders are given 1 injection a week for 3 weeks of either KET or the sedative agent to determine if beneficial effects of KET are maintained, and to assess duration of its benefits after repeated administration. The genetic profile of patients for a substance promoting contacts between cells and brain will be determined to investigate if response to KET could be predicted with that blood test. This substance, as well as several chemicals that produce inflammation, will also be measured in the blood to investigate their role in the effect of KET. Patients will receive, in total, no more than the equivalent of two to three anesthetic dose of KET. Results from this study will help establish the beneficial effects of a single KET injection as a rapid intervention for major depression, and to investigate the possibility of obtaining a prolonged antidepressant effect with repeated injections.


Condition Intervention Phase
Treatment-resistant Depression
Drug: Ketamine
Drug: Midazolam
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2 Optimization of the Antidepressant Action of Ketamine in Treatment-Resistant Depression and Investigations on Its Mechanism of Action

Resource links provided by NLM:


Further study details as provided by University of Ottawa:

Primary Outcome Measures:
  • Efficacy of Ketamine over Midazolam in double blind study for efficacy of relief for Major Depressive Disorder [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Phase 1 double blind treatment with Ketamine or Midazolam then crossover. Will assess efficacy of each for relief of Major Depressive Symptoms through assessment using the HAMD17.


Secondary Outcome Measures:
  • Ketamine for use in relief of Major Depressive Disorder over repeated administration [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Repeated infusion of ketamine in phases 2 and 3 to determine efficacy over extended treatment period.We will assess effectiveness for treatment of depression by administering the Montgomery-Asberg Depression Rating Scale (MADRS)to assess severity of depressive symptoms. MADRS will be given before and after each infusion and at follow up visits to monitor changes.

  • To determine the role of genetic polymorphisms in the participants response to ketamine infusion [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    Patients will be genotyped for a VAL/MET polymorphism for the brain-derived neutrophic factor (BDNF)gene to see whether presence or absence of the polymorphism mediates their antidepressant response.


Other Outcome Measures:
  • Cortisol, melatonin, and inflammatory mediators will be assessed to examine changes occurring during treatment with ketamine [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    Pro-inflammatory mediators and cortisol are generally elevated in depression while melatonin is decreased. These anomalies are typically restored with effective treatments. This will be investigated in the light of the rapid antidepressant effect of ketamine.

    During phase 1, patients will provide samples of saliva for morning melatonin and salivary cortisol at 1)Randomization, 2)Phase 2,infusion 6, 3)Phase 3, infusion 4. Collected for 2 days: Immediately upon waking;30 minutes later;1 hour later;Mid-day.

    Inflammatory mediators will be assessed to determine changes occurring throughout treatment. Two blood samples will be drawn at each of the following study visits: Randomization;Phase 2, infusion 6;Phase 3, infusion 4 We will examine C-reactive protein, IL-1β, IL-2, IL-6, IL-8, IL-12, IFN-γ, TNF-α, and anti-inflammatory factors IL-4 and IL-10.


  • Effects of ketamine infusion compared to midazolam [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    A clinician will evaluate their clinical status prior to the infusion, using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Intensity-Severity (CGI-S) and the patients will rate themselves using the Quick Inventory Depressive Symptoms-Self-report (QIDS-SR)105 and a self-report questionnaire rating suicidality. The patients will be assessed using the Brief Psychiatric Rating Scale-positive symptom scale at baseline (before the infusion), time 0 (immediately after infusion is complete), then at 60 and 120 minutes post time 0. The CGI-Improvement (CGI-I) will be used to obtain a clinical evaluation of overall change of their condition after two hours before discharging the patients two hours after the infusion. We will compare the scores on the scales used in ketamine infusion verses midazolam to evaluate whether ketamine is superior but also whether midazolam is an effective control (patients feel some effects similar to ketamine infusion)


Estimated Enrollment: 63
Study Start Date: May 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
During Phase 1 patients will be randomly assigned to receive ketamine or active placebo.
Drug: Ketamine
Intravenous Bolus infusion Ketamine Hydrochloride 0.50 mg/mL over 40 minutes
Other Names:
  • Ketamine Hydrochloride
  • Kevlar
Active Comparator: Midazolam
In phase 1 patients will be randomized to receive active placebo
Drug: Midazolam
Bolus infusion of Midazolam Hydrochloride 1 mg/mL over 40 minutes
Other Names:
  • Midazolam Hydrochloride
  • Midazolam HCL

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Only participants from the Ottawa area will be considered
  • Provision of written informed consent before initiation of any study- related procedures.
  • Documented primary Axis I clinical diagnosis meeting criteria from the DSM-IV13 for MDD, as confirmed by the MINI.98
  • Failure to respond adequately to at least two antidepressant medication trials and two augmentation strategies. One augmentation strategy may include a noradrenergic dose of venlafaxine (225 mg/day) or duloxetine (120 mg/day), given their dual mechanism of action99,100 and a 12-week cognitive behavioural or interpersonal therapy
  • MADRS total score of ≥ 25 at screening and randomization, with no more than 20% improvement between these two visits.
  • Female subjects of childbearing potential must have a negative urine pregnancy test at enrolment (Visit 1) and be willing to use a reliable method of birth control (i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation) during the study.
  • Abstain from consuming grapefruit juice (a potent 3A4 cytochrome inhibitor) on the day of the infusions as it may slow down the elimination of midazolam and possibly ketamine.
  • Be able to understand and comply with the requirements of the study, as judged by the investigator(s).

Exclusion Criteria:

  • Subjects with a diagnosis of DSM-IV Axis II disorder which has a major impact on the subject's current psychiatric status.
  • Depression secondary to stroke, cancer or other severe medical illnesses.
  • Prior or current substance or alcohol abuse or dependence (except for caffeine or nicotine dependence), as defined in DSM-IV criteria.
  • A positive drug screen.
  • Unwilling to maintain their current antidepressant regimen. infusions.
  • Unwilling or able to hold benzodiazepines on the day prior and that of the Unwilling to discontinue any narcotic for a minimum of 5 drug half-lives prior to infusions.
  • Pregnant or lactating, or is of childbearing potential and not willing to use an approved method of contraception during the study.
  • Evidence of clinically relevant disease, e.g., renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome.
  • A clinical finding that is unstable or that, in the opinion of the investigator(s), would be negatively affected by the study medication or that would affect the study medication (e.g., diabetes mellitus, hypertension, unstable angina).
  • Liver function tests AST and ALT three times the upper normal limit at screening.
  • Uncorrected hypothyroidism or hyperthyroidism. Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 30 days prior to enrolment (Visit 1).
  • Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator(s).
  • ECG results considered clinically significant as determined by the investigator(s).
  • History of seizure disorder, except febrile convulsions.
  • Subjects who in the investigator(s) opinion will require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 2 months prior to Visit 2.
  • Known history of intolerance or hypersensitivity to ketamine or midazolam.
  • Any other condition that, in the opinion of the investigator(s) would adversely affect the subject's
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01945047

Contacts
Contact: Wendy Fusee, RN 613-722-6521 ext 7828 wendy.fusee@theroyal.ca
Contact: Lisa Batten, Master 613-722-6521 ext 6971 lisa.batten@theroyal.ca

Locations
Canada, Ontario
Institute of Mental Health Research, Royal Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1Z 7K4
Contact: Wendy Fusee, RN    613-722-6521 ext 7828    wendy.fusee@theroyal.ca   
Contact: Lisa batten, Master    613-722-6521 ext 6971    lisa.batten@theroyal.ca   
Principal Investigator: Pierre Blier, M.D. Ph.D         
Sponsors and Collaborators
University of Ottawa
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Pierre Blier, M.D, Ph.D University of Ottawa, Institute of Mental Health Research
  More Information

No publications provided

Responsible Party: Pierre Blier, Endowed Chair and Director of Mood Disorders Research Unit, University of Ottawa
ClinicalTrials.gov Identifier: NCT01945047     History of Changes
Other Study ID Numbers: REB2012023
Study First Received: May 22, 2013
Last Updated: May 6, 2014
Health Authority: Canada: Canadian Institutes of Health Research
Canada: Health Canada

Keywords provided by University of Ottawa:
depression
treatment
ketamine
ottawa
treatment-resistant
infusion

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Mood Disorders
Mental Disorders
Depression
Behavioral Symptoms
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on September 30, 2014