To Test the Potential Efficacy of Repeated Intranasal Administration of Ketamine as a Treatment for PTSD

PTSD Clinical Trial

Official title:

Randomized Controlled Trial of Repeated Dose Ketamine in Post Traumatic Stress Disorder (PTSD)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02398136
• Other study ID #: GCO 14-1781
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• First received: November 7, 2014
• Last updated: March 19, 2015
• Start date: December 2014
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see whether ketamine, when given repeatedly via the nose (intranasally), can produce a quick and persistent improvement in PTSD symptoms. At higher doses, ketamine has been used for many years as an anesthetic for medical procedures, and at lower doses may be an effective treatment in patients with major depression and PTSD.

Description:

The objective of the present research protocol, a parallel-arm, double-blind, randomized controlled clinical trial, is to test the efficacy of repeated intranasal administration of the glutamatergic NMDA receptor antagonist ketamine in providing (1) rapid relief of and (2) sustained improvement in core PTSD symptoms and co-morbid depressive symptoms in patients with chronic PTSD. The effects of ketamine will be compared with those of repeated intranasal administration of the benzodiazepine anesthetic midazolam, which mimics some of the acute subjective effects of ketamine but is expected to have lesser or less sustained anxiolytic effect, and no sustained antidepressant effect.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men or women, 18-65 years of age;

• Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;

• Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS -this is done to ensure at least moderate severity and to safeguard against high placebo response rates;

• Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);

• Women of childbearing potential must have a negative pregnancy test at screening and prior to each intranasal administration;

• Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).

Exclusion Criteria:

• Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);

• Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;

• Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;

• Patients with uncorrected hypothyroidism or hyperthyroidism;

• Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first intranasal administration day;

• Use of evidence-based individual psychotherapy (such as prolonged exposure) during the study;

• History of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;

• History of one or more seizures without a clear and resolved etiology;

• History of (hypo)mania;

• Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;

• Drug or alcohol abuse or dependence within the preceding 3 months; a rather narrow time period was chosen, however, in order to allow participation by individuals with a history of substance abuse or dependence problems that could be secondary to their PTSD, and to more closely approximate patients seen in real-world settings; this is the same period of time that we used in our recently completed study of IV ketamine for PTSD.

• Previous recreational use of ketamine or PCP;

• Current diagnosis of bulimia nervosa or anorexia nervosa;

• Diagnosis of schizotypal or antisocial personality disorder (since these are known to reduce the possibility of study completion); other Axis II diagnoses will be allowed;

• Patients judged clinically to be at serious and imminent suicidal or homicidal risk.

• A blood pressure of one reading over 160/90 or two separate readings over 140/90 at screen or baseline visits

• Patients who report current treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to randomization; patients taking stable doses of antidepressant medication for 3 months prior to randomization will be allowed.

• For subjects who may participate in the MRI portion of the study, claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• PTSD
• Stress Disorders, Post-Traumatic

Intervention

Drug:
• Ketamine

• Midazolam

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Adriana Feder

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of Events Scale-Revised (IES-R)	The IES-R is used to self-report measures of stress reactions to traumatic events. It measures both intrusion and avoidance.	24 hours	No
Secondary	Clinician Administered PTSD Scale (CAPS)	The CAPS is a structured clinical interview designed to assess the essential features of PTSD.	up to 4 weeks	No
Secondary	Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)	The QIDS-SR is a 16-item self-rated instrument designed to assess the severity of depressive symptoms present in the past seven days.	24 hours	No
Secondary	Montgomery Asberg Depression Rating Scale (MADRS)	The MADRS is a 10-item instrument used for the evaluation of depressive symptoms and for the assessment of any changes to those symptoms.	24 hours	No
Secondary	Patient-Rated Inventory of Side Effects (PRISE)	PRISE is a 7-item self report used to qualify side effects by identifying and evaluating the tolerability of each symptoms.	24 hours	No
Secondary	Sheehan Disability Scale (SDS)	The SDS is a 10 point visual analog scale developed to assess functional impairment.	24 hours	No