Back to resultsKetamine Infusion for Comorbid PTSD and Chronic Pain
Primary Purpose
PTSD, Chronic Pain
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
A single low dose ketamine infusion as compared to the IV infusion of active placebo - ketorolac on chronic pain and PTSD symptoms.
Sponsored by
About this trial
This is an interventional treatment trial for PTSD focused on measuring PTSD, chronic pain, ketamine infusion
Eligibility Criteria
Inclusion Criteria:
Veterans with chronic pain as defined by having any chronic pain beyond 6 months in duration with and without PTSD diagnoses (participants must meet DSM-V criteria for current post-traumatic stress disorder (PTSD) and have received a diagnosis of PTSD greater than or equal to 3 months prior to assessment); they also will be either free of concomitant use of psychotropic and/or pain medications for at least 6 weeks or on stable doses of those medications within the last 6 weeks prior to randomization and for the duration of the study; if applicable, current frequency and duration of psychotherapy sessions must remain stable for at least 6 weeks prior to beginning of the study.
Exclusion Criteria:
Inability to speak English, inability or unwillingness to provide written informed consent; moderate-to-severe cognitive impairment (Mini-Mental State Examination scores<20 administered by a trained clinician); current or lifetime history of psychotic or bipolar disorder; current bulimia or anorexia nervosa, alcohol abuse or dependence in the previous 3 months; serious unstable medical illness or sleep apnea; HTN, prolonged QT interval, peptic ulcer disease or recent history of GI-bleed, renal insufficiency, active substance use disorder, active suicidal or homicidal ideation on presentation; pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study.
Sites / Locations
- Ann Arbor VA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Experimental
Active Comparator
Arm Label
Chronic pain with PTSD+IV ketamine infusion
Chronic pain with PTSD+IV ketorolac infusion
Chronic pain without PTSD+IV ketamine infusion
Chronic pain without PTSD+IV ketorolac infusion
Arm Description
Outcomes
Primary Outcome Measures
Impact of Event Scale-Revised (IES-R)
Severity of PTSD symptoms; items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88); higher scores mean worse symptoms
Visual Analogue Scale (VAS)
Severity of chronic pain symptoms; using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100; a higher score indicates greater pain intensity.
Secondary Outcome Measures
Impact of Event Scale-Revised (IES-R)
Severity of PTSD symptoms; items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88); higher scores mean worse symptoms
Visual Analogue Scale (VAS)
Severity of chronic pain symptoms; using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100; a higher score indicates greater pain intensity.
Brief Pain Inventory (Short Form)
Severity of pain, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week; No scoring algorithm, but "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity (a range of 0-10, with 10 being worse scores); the arithmetic mean of the seven interference items can be used as a measure of pain interference (a range of 0-10, with 10 being worse scores). The total score is reported for severity items and interference items, which range from 0-40 and 0-70, respectively. Higher values represent worse outcome.
Full Information
NCT ID
NCT04322968
First Posted
March 24, 2020
Last Updated
November 30, 2020
Sponsor
VA Ann Arbor Healthcare System
Collaborators
University of Michigan
1. Study Identification
Unique Protocol Identification Number
NCT04322968
Brief Title
Ketamine Infusion for Comorbid PTSD and Chronic Pain
Official Title
Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain Patients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
January 9, 2018 (Actual)
Primary Completion Date
June 4, 2019 (Actual)
Study Completion Date
June 4, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Ann Arbor Healthcare System
Collaborators
University of Michigan
4. Oversight
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
5. Study Description
Brief Summary
The purpose of the study is to investigate the effectiveness of low dose IV ketamine infusion in the treatment of patients with PTSD and comorbid chronic pain.
Hypothesis: A single ketamine infusion should be associated with significantly greater reduction in core PTSD symptom levels after the treatment and such an effect is not only due to its analgesic properties but also through unknown mechanism of action that maybe related to NMDA/AMPA receptor modulation.
Detailed Description
To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with PTSD, are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain about one third suffer from comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of chronic pain, however they have not been studied in comorbid population and under rigorous control conditions. The investigators compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in chronic pain patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, 1 day and 7 days after the infusion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PTSD, Chronic Pain
Keywords
PTSD, chronic pain, ketamine infusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patient with and without PTSD were randomized to receive either ketamine or ketorolac. Single IV infusion of ketamine hydrochloride (0.5 mg/kg) was administered over 40 minutes. Ketorolac 15 mg was reconstituted in 500 cc of normal saline administered over 40 minutes.
Masking
ParticipantOutcomes Assessor
Masking Description
All study personnel, including rater, patients, and data analysts, were blinded to randomization order. Only the anesthesiologist performing the infusion was not blinded in order to prepare for possible side effects of each medication.
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chronic pain with PTSD+IV ketamine infusion
Arm Type
Experimental
Arm Title
Chronic pain with PTSD+IV ketorolac infusion
Arm Type
Active Comparator
Arm Title
Chronic pain without PTSD+IV ketamine infusion
Arm Type
Experimental
Arm Title
Chronic pain without PTSD+IV ketorolac infusion
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
A single low dose ketamine infusion as compared to the IV infusion of active placebo - ketorolac on chronic pain and PTSD symptoms.
Intervention Description
Subjects were randomized into 4 treatment groups: chronic pain subjects treated with ketorolac, chronic pain subjects treated with ketamine, chronic pain+PTSD subjects treated with ketorolac, and chronic pain+PTSD subjects treated with ketamine.
Primary Outcome Measure Information:
Title
Impact of Event Scale-Revised (IES-R)
Description
Severity of PTSD symptoms; items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88); higher scores mean worse symptoms
Time Frame
24 hrs post-infusion
Title
Visual Analogue Scale (VAS)
Description
Severity of chronic pain symptoms; using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100; a higher score indicates greater pain intensity.
Time Frame
24 hrs post-infusion
Secondary Outcome Measure Information:
Title
Impact of Event Scale-Revised (IES-R)
Description
Severity of PTSD symptoms; items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88); higher scores mean worse symptoms
Time Frame
1 week post-infusion
Title
Visual Analogue Scale (VAS)
Description
Severity of chronic pain symptoms; using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100; a higher score indicates greater pain intensity.
Time Frame
1 week post-infusion
Title
Brief Pain Inventory (Short Form)
Description
Severity of pain, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week; No scoring algorithm, but "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity (a range of 0-10, with 10 being worse scores); the arithmetic mean of the seven interference items can be used as a measure of pain interference (a range of 0-10, with 10 being worse scores). The total score is reported for severity items and interference items, which range from 0-40 and 0-70, respectively. Higher values represent worse outcome.
Time Frame
1 week post-infusion
Other Pre-specified Outcome Measures:
Title
Patient-Rated Inventory of Side Effects (PRISE20)
Description
Patient self report used to qualify side effects by identifying and evaluating the tolerability of each symptoms; 20 items; higher scores mean worse side effects
Time Frame
baseline-1 week post-infusion
Title
Clinician-Administered Dissociative States Scale (CADSS)
Description
Dissociative, psychotomimetic, and manic symptoms; 27-item scale with 19 subject-rated items and 8 items scored by an observer; higher scores mean worse present-state dissociative symptomatology
Time Frame
baseline-1 week post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Veterans with chronic pain as defined by having any chronic pain beyond 6 months in duration with and without PTSD diagnoses (participants must meet DSM-V criteria for current post-traumatic stress disorder (PTSD) and have received a diagnosis of PTSD greater than or equal to 3 months prior to assessment); they also will be either free of concomitant use of psychotropic and/or pain medications for at least 6 weeks or on stable doses of those medications within the last 6 weeks prior to randomization and for the duration of the study; if applicable, current frequency and duration of psychotherapy sessions must remain stable for at least 6 weeks prior to beginning of the study.
Exclusion Criteria:
Inability to speak English, inability or unwillingness to provide written informed consent; moderate-to-severe cognitive impairment (Mini-Mental State Examination scores<20 administered by a trained clinician); current or lifetime history of psychotic or bipolar disorder; current bulimia or anorexia nervosa, alcohol abuse or dependence in the previous 3 months; serious unstable medical illness or sleep apnea; HTN, prolonged QT interval, peptic ulcer disease or recent history of GI-bleed, renal insufficiency, active substance use disorder, active suicidal or homicidal ideation on presentation; pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study.
Facility Information:
Facility Name
Ann Arbor VA Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Local IRB has conducted informed consent audit for the study and the investigators have been compliant with it.
Citations:
PubMed Identifier
10937428
Citation
Asmundson GJ, Bonin MF, Frombach IK, Norton GR. Evidence of a disposition toward fearfulness and vulnerability to posttraumatic stress in dysfunctional pain patients. Behav Res Ther. 2000 Aug;38(8):801-12. doi: 10.1016/s0005-7967(99)00101-1.
Results Reference
background
PubMed Identifier
15939839
Citation
Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):617-27. doi: 10.1001/archpsyc.62.6.617. Erratum In: Arch Gen Psychiatry. 2005 Jul;62(7):709. Merikangas, Kathleen R [added].
Results Reference
background
PubMed Identifier
24740528
Citation
Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.
Results Reference
background
PubMed Identifier
29727073
Citation
Albott CS, Lim KO, Forbes MK, Erbes C, Tye SJ, Grabowski JG, Thuras P, Batres-Y-Carr TM, Wels J, Shiroma PR. Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. J Clin Psychiatry. 2018 May/Jun;79(3):17m11634. doi: 10.4088/JCP.17m11634.
Results Reference
background
PubMed Identifier
19604642
Citation
Sigtermans MJ, van Hilten JJ, Bauer MCR, Arbous SM, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-311. doi: 10.1016/j.pain.2009.06.023. Epub 2009 Jul 14.
Results Reference
background
PubMed Identifier
21482474
Citation
Noppers I, Niesters M, Swartjes M, Bauer M, Aarts L, Geleijnse N, Mooren R, Dahan A, Sarton E. Absence of long-term analgesic effect from a short-term S-ketamine infusion on fibromyalgia pain: a randomized, prospective, double blind, active placebo-controlled trial. Eur J Pain. 2011 Oct;15(9):942-9. doi: 10.1016/j.ejpain.2011.03.008. Epub 2011 Apr 11.
Results Reference
background
Learn more about this trial
Ketamine Infusion for Comorbid PTSD and Chronic Pain
We'll reach out to this number within 24 hrs