Double Blind Placebo Controlled Study of Outpatient Intravenous Ketamine for the Treatment of CRPS
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|ClinicalTrials.gov Identifier: NCT00579085|
Recruitment Status : Completed
First Posted : December 21, 2007
Last Update Posted : June 17, 2010
|First Submitted Date ICMJE||December 20, 2007|
|First Posted Date ICMJE||December 21, 2007|
|Last Update Posted Date||June 17, 2010|
|Study Start Date ICMJE||September 2006|
|Actual Primary Completion Date||September 2008 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS by a 30% pain reduction post treatment [ Time Frame: Patients will be evaluated for three months after treatment ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00579085 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Lenght of relief of pain [ Time Frame: When and if pain returns to pre treatment levels ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Double Blind Placebo Controlled Study of Outpatient Intravenous Ketamine for the Treatment of CRPS|
|Official Title ICMJE||Double Blind Placebo Controlled Study of Outpatient Intravenous Ketamine for the Treatment of CRPS|
|Brief Summary||Complex Regional Pain Syndrome is a debilitating and extremely difficult to treat condition. There is a large body of evidence demonstrating the therapeutic value of N-methyl-D-aspartate (NMDA)-receptor antagonists in CRPS. The NMDA antagonist ketamine has been shown to be effective in the treatment of CRPS, resulting in complete remission of the disease in some patients. The purpose of this study is to evaluate intravenous outpatient infusion of sub-anesthetic doses of ketamine for the treatment of CRPS. A thorough evaluation of this procedure, providing information into the degree of relief and which of the constellation of RSD symptoms are best alleviated by this procedure would result in the optimization of this therapy for the treatment of CRPS.|
Prior to treatment, after informed consent is obtained, each subject will be randomized into the ketamine or placebo (normal saline) infusion group. Both the patient and all other individuals involved in the study will be blinded as to the treatment except Guillermo Alexander PhD who will be responsible for the randomization and Margaret Rose RN who will be responsible for preparing the infusion solution. The patient will then receive a complete neurological examination and will be asked to complete a short form McGill and Quality of life questionnaires (Attachment 1).
Two weeks before treatment, 2 week and 3 months post treatment the following sensory and motor tests will be performed.
Thermal Detection Thresholds: Cool detection thresholds, which are mediated via A fibers and warm detection thresholds, which are mediated by small unmyelinated C fibers, will be determined using the TSA-II NeuroSensory Analyzer (Medoc Advanced Medical Systems U.S., Minneapolis, MN). The device consists of a computer controlled thermoelectric probe with a surface area of 9 cm2 that is attached using a velcro strap to the area of skin to be tested (thenar eminence and hypothenar eminence in the hands and the dorsal foot). For each trial the thermal stimulator starts at the thermo-neutral baseline temperature of 32oC, and increases for warming thresholds, or decreases for cooling thresholds, linearly at a rate of 1oC per second, until the subject pushes a button that stops and records the temperature and returns the unit to baseline temperature. Three trials are averaged for cool and for warm threshold for each site tested.
Thermal Pain: Thermal pain tolerance will be determined at the same sites and using the same method described above for thermal detection thresholds. The only difference is that for thermal pain trials, the subject will be instructed to push the control button (which immediately resets the stimulator back to baseline temperature) when the thermal stimulus (cold or hot) becomes painful. The TSA-II hardware automatically resets if the temperature reaches -10oC (for cooling) or 50oC (for heating) and the control button has not been pushed. This temperature range has been determined to not cause damage to skin or underlying tissue.
Dynamic Mechano-allodynia: Dynamic mechano-allodynia will be determined by stroking the skin three times within 5 seconds at a rate of 5 cm/sec with a 2.5 cm wide standard foam paintbrush. Allodynia severity will be measured on the subject's response using a numerical rating scale. The subject reports both the amount of pain on a 0-10 scale (0: no pain; 10: worst pain ever experienced) and the extent to which the sensation spread.
Static Mechano-allodynia and Temporal Summation: Static mechano-allodynia and temporal summation will be determined by pin-prick with a standard safety pin once every three seconds for a total of 5 times. The subject will be instructed to report the level of pain on a 0-10 scale (0: no pain; 10: worst pain ever experienced) and the extent to which the sensation spread after each repetition. The test will stop if the subject reports unacceptable pain at any point during the test.
Deep pressure pain thresholds: Deep pressure pain thresholds will be determined with a pressure algometer (Wagner Instruments, Greenwich, CT) which is a hand held device with a 1cm2 rub¬ber tip capable of measuring applied pressures of 0-5 kg. The device is held at a 90o angle to the body surface being tested. The pressure is gradually increased by 1 kg/second until the subject reports that the stimulus is painful or a pressure of 4 kg/cm2 has been reached. In the upper extremity thresholds to pain will be determined at: 1)second costosternal joint; 2) acromioclavicular joint; 3) lateral epicondyle; 4) radial styloid; 5) ulnar styloid; 6) second metacarpal; 6) fifth metacarpal. In the lower extremity thresholds to pain will be determined at: 1) greater trochanter; 2) lateral femoral condyle; 3) tibial tubercle; 4) mid shin; 5) medial malleolus; 6) lateral malleolus; 7) first metatarsal; 8) fifth metatarsal.
Quantification of Motor Function (finger tap): Finger tap rate will be determined using a computer program developed by our group. The subject is instructed to press the spacebar of a standard computer keyboard as fast as possible with the index finger of each hand respectively for 30 seconds. The program determines the rate and plots the results.
Cutaneous Temperature: Skin temperature will be measured by use of an infra-red thermometer (Dermatemp Infrared Temperature Scanner, model DT-1001, Exergen Corp., Watertown, MA)
A pregnancy test will be administered to all females of child bearing potential and blood will also be drawn for SMA-20, CBC w/ Differential and a full thyroid panel. All subjects will be asked to wear an activity watch until the treatment begins (two week). This watch (Attachment 2) will evaluate the subject's level of activity and at random programmed intervals records the subject's pain level for the two weeks prior to treatment. This is accomplished by sounding a tone at which time the subject is instructed to presses a key pad and enter a number from 0-10 (0 = no pain and 10 = unbearable pain). The patient will be asked to complete the short form McGill and Quality of life questionnaires weekly until the start of the infusions.
On the first day of treatment but prior to the start of the infusions, the patient will be weighed, undergo a neurologic exam, have vital signs evaluated and have an intravenous line inserted.
On all ten treatment days, patients on both the ketamine and placebo groups are placed on the cardiac monitor for cardiac rhythm, blood pressure, pulse and oxygen saturation monitoring. In addition, Clonidine (0.1 mg, po) and Versed (4 mg, iv) will be administered. Clonidine has been shown, in animals, to potentiate the neuropathic pain-relieving action of NMDA receptor blockers like ketamine while preventing their neurotoxic side effects. Versed at this dose, provides mild sedation and relieves anxiety.
All patients will be infused intravenously with 100 ml of normal saline with or without ketamine for four hours (25 ml/hr) daily for 10 days. The maximum intravenous ketamine infusion dose for this study will be 0.35 mg/kg/hr, not to exceed 25 mg/hr (100 mg of ketamine over a 4 hour period). On the first day, the intravenous ketamine infusion will be set to 50% of the maximum rate. On the second day, the intravenous ketamine infusion will be increased to 75% of the maximum rate. On the third day, the intravenous ketamine infusion will be increased to the maximum rate. The daily ketamine infusion rate is maintained at this level for the duration of the ten day study.
CONSIDERATIONS: (Other Treatments and Meds)
Glycopyrrolate (Robinul) Initially 1mg TID then maintenance dose BID prn
Ativan 1mg - HAVE AVAILABLE prn Continued use of current medications with the exception of NMDA receptor blockers such as amantadine, memantine, Magnesium sulfate.
Administer other adjuncts prn O2 2-3 L/min. via Nasal Cannula - HAVE AVAILABLE prn
Ketamine Level (red top tube) on infusion days 1, 5, 6 and 10.
NURSING CARE & ORDERS:
During the IV Ketamine Infusion:
Continuous cardiac monitoring, Pulse oximetry with q 1 hr blood pressure monitoring V/S q 1 hr Versed (2 mg iv) administration may be repeated two hours into or at the completion of the infusion.
Patient can leave infusion chair with assistance for bathroom visit. Patient is allowed to bring head set (music) or a book to read. No cell phones or laptop computers are allowed.
Following the last (10th) infusion, the patient will be seen at two weeks then monthly at the Neurology Pain Clinic for the following 3 months. All subjects will be asked to wear an activity watch from the time of the last infusion until the two week post treatment visit. Patients will be instructed to complete the
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||Complex Regional Pain Syndrome|
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Actual Study Completion Date ICMJE||November 2009|
|Actual Primary Completion Date||September 2008 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 65 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00579085|
|Other Study ID Numbers ICMJE||16078-2-1 version 2|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Dr. Robert J. Schwartzman MD, Drexel University College of Medicine|
|Study Sponsor ICMJE||Drexel University College of Medicine|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||Drexel University|
|Verification Date||June 2010|
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