Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Open Study of the Neurobiological Effects of Intranasal Ketamine in Children and Adults With Bipolar Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05209217
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : January 27, 2022
Sponsor:
Collaborator:
Juvenile Bipolar Research Foundation
Information provided by (Responsible Party):
Martin H Teicher, Mclean Hospital

Tracking Information
First Submitted Date October 26, 2018
First Posted Date January 26, 2022
Last Update Posted Date January 27, 2022
Actual Study Start Date June 4, 2019
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 25, 2022)
  • BOLD fMRI response in amygdala [ Time Frame: Prior to and 2-3 hours following ketamine administration ]
    Change in BOLD measured by functional Magnetic Resonance Imaging (fMRI) to images of threatening versus neutral facial expressions.
  • BOLD fMRI response in posterior insula [ Time Frame: Prior to and 2-3 hours following ketamine administration ]
    Correlation between BOLD measured by functional Magnetic Resonance Imaging (fMRI) and degree of cold stimulation of non-dominant hand.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 25, 2022)
  • Functional connectivity between amygdala and insula [ Time Frame: Prior to and 2-3 hours following ketamine administration ]
    Seed-to-seed and seed-to-voxel functional connectivity analysis of rs-fMRI data.
  • EEG spectral activity measures [ Time Frame: Prior to and 2-3 hours following ketamine administration ]
    Absolute and relative power in low beta (15-26), high beta (28-40), low gamma (42-53) and high gamma (55-67) frequency bands using 32-channel Electrical Geodesics, Inc. EEG.
  • Profile of Mood State (POMS) scale. [ Time Frame: Prior to and 2-3 hours following ketamine administration ]
    Ratings of tension and total mood score on the POMS.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Open Study of the Neurobiological Effects of Intranasal Ketamine in Children and Adults With Bipolar Disorder
Official Title Open Study of the Neurobiological Effects of Intranasal Ketamine in Children and Adults With Bipolar Disorder - Fear of Harm Phenotype
Brief Summary

Aim 1: Test the hypothesis that participants with Bipolar Disorder - Fear of Harm Phenotype have an enhanced amygdala fMRI response to fearful threatening stimuli, increased resting beta and gamma EEG spectral activity in temporal leads and blunted posterior insula response to cold when partially withdrawn from ketamine with normalization of these responses following intranasal administration of ketamine.

Aim 2. Test the hypothesis that ketamine alters response to fearful-threatening visual stimuli and cold sensation by altering functional connectivity of the amygdala and insula with the hypothalamus, thalamus, hippocampus and ventromedial prefrontal cortex, and identify specific alterations that correlate with degree of pre-post ketamine change.

Aim 3. Test the hypothesis that low-dose medicinal ketamine, unlike high-dose recreation ketamine, is not associated with an increase in number of focal areas of abnormality on morphometric scans based on duration of use.

Detailed Description Clinically, the Fear of Harm phenotype is characterized by early age of onset, severe mood swings, treatment resistance, separation anxiety, fearful-aggressive obsessions, parasomnias (e.g. night-terrors) and thermal dysregulation (Papolos et al. 2009). These youth typically received little benefit from standard treatments (i.e., antipsychotic medication and mood stabilizers) often wind up home-schooled due to excessive fears of the school environment and frequently require multiple periods of inpatient care (Papolos et al. 2009; Papolos et al. 2013). Key features seen in FOH that distinguish these youths from other youths with BD include fear sensitization and thermal dysregulation. Children with FOH often experience thermal discomfort (e.g., feeling hot, excessive sweating) in neutral ambient temperature conditions, as well as no discomfort during exposure to the cold, and alternate noticeably between being excessively hot in the evening and cold in the morning (Murphy, Frei, and Papolos 2014). Ketamine, an NMDA receptor antagonist was selected as a potential treatment for FOH because of its effectiveness in the reduction of fear sensitization and capacity to dose-dependently lower body temperature in animal studies, and has been found to be clinically efficacious in the treatment of FOH (Papolos et al. 2018; Papolos et al. 2013). There are two main reasons for proposing to conduct a neuroimaging study. First, intranasal ketamine can produce an almost immediate improvement in clinical state. This makes it possible to scan a subject whose dose of ketamine has largely worn off in order to assess blood flow and functional connectivity and then to rescan the individual within hours of receiving intranasal ketamine in order to correlate degree of clinical improvement with alterations in blood flow and connectivity. This will provide information on both the neurobiological basis of ketamine response and information on the possible biological underpinnings of FOH. Second, there is some concern, based on a report of examining brain scans in chronic ketamine abusers, that ketamine in daily doses 10X higher than clinically prescribed every 3-4 days can produce some evidence for structural brain damage4. Hence, it would be valuable to scan individuals undergoing long term treatment with intranasal ketamine to rule out or monitor for pathological changes in brain structure.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population

Total sample size will be 20 subjects, with approximately equal number of males and females.

Subjects recruited for the study will be between 14-40-years-of-age who meet DSM-5 criteria for Bipolar Disorder, Papolos criteria for FOH Phenotype, have been taking intranasal ketamine for at least two months

Condition Bipolar Disorder
Intervention Drug: Ketamine
Intranasal administration of their customary prescribed dose
Study Groups/Cohorts Participant Group
Participants will all have history of good to excellent clinical response to intranasal ketamine for at least two months and on a treatment schedule varying from use every other day to every fifth day. Participants will be tested one or two days beyond their customary administration date and again 2-3 hours after their administration of ketamine.
Intervention: Drug: Ketamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: January 25, 2022)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 15, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Males and Females
  • Age 14 - 40 years
  • Clinical diagnosis of Bipolar Disorder -Fear of Harm Phenotype
  • Meets Papolos criteria for FOH based on independent interviews.
  • Taking intranasal ketamine for at least 2 months.
  • Must be on an every three or every four-day dosing regimen
  • Dosage will not exceed 300 mg per dosing interval.
  • Willing to delay ketamine dose by 2 days past their prescribed dosing interval
  • Prior experience having tolerated this degree of delay.
  • Willing to participate in daily assessments during period of ketamine withdrawal prior to traveling to Belmont ,MA.
  • Willing to provide urine sample to screen for drugs of abuse (all participants and pregnancy in females.)

Exclusion Criteria:

  • Any psychiatric hospitalization within the past 6 months
  • Lifetime history of suicide attempts
  • Co-occurring substance use disorders
  • Any change in concomitant medications within the last 2 months
Sex/Gender
Sexes Eligible for Study: All
Ages 14 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Elizabeth A Bolger, MA 617-855-2964 lbolger@mclean.harvard.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT05209217
Other Study ID Numbers 2017P001822
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: There is no plan to share with other researchers
Current Responsible Party Martin H Teicher, Mclean Hospital
Original Responsible Party Same as current
Current Study Sponsor Mclean Hospital
Original Study Sponsor Same as current
Collaborators Juvenile Bipolar Research Foundation
Investigators
Principal Investigator: Martin H Teicher, MD, PhD Mclean Hospital
PRS Account Mclean Hospital
Verification Date January 2022