Effectiveness of Ketamine in Malignant Neuropathic Pain Relief

NCT ID: NCT01951911

Last Updated: 2017-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2016-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

To see whether the addition of low-dose ketamine to a subcutaneous morphine infusion improves analgesia in patients with neuropathic cancer pain.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Patients with cancer pain judged to have a neuropathic component and receiving pain treatment with a subcutaneous infusion of morphine will be included in a randomized, double blind, placebo-controlled, crossover study. All patients will be recruited from hospital wards (Haukeland University Hospital, Bergen). In the case of patient withdrawal or dropout, new patients will be recruited so that the total number of patients completing the study will be 20. Data from patients not completing the study will solely be used to provide information about adverse effects.

The basic treatment with subcutaneous morphine infusion will be supplemented with a separate subcutaneous infusion of ketamine 1 mg/kg/ 24 hours or NaCl 9 mg/ml (placebo).

After 48 hours (phase 1) there will be a "wash-out" period of minimum 10 hours to minimize carryover effects before the treatment is replaced by the alternative treatment for a further 48 hours (phase 2) in a standard crossover design. The treatment duration is based on ketamine's short plasma half-life which is less than 2 hours after initial equilibration.

Pain intensity (using NRS) will be recorded at rest and on movement x 4 daily. Rescue medication in the form of morphine subcutaneous bolus may be given to the patient as required. There will be a" lockout" time of 1 hour which means that the rescue dose of morphine can be repeated every 60 minutes if necessary, providing the patient is awake and has a respiratory rate of 8 or more per minute.Randomization will be performed by Haukeland University Hospital Pharmacy. The study drug/ placebo will also be prepared by the hospital pharmacy according to a standard instruction.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Pain, Intractable

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ketamine

Ketamine 1 mg per kg per 24 hours as subcutaneous infusion via syringe driver for 48 hours.

Group Type ACTIVE_COMPARATOR

Ketamine

Intervention Type DRUG

Patients will receive either ketamine as subcutaneous infusion or placebo as subcutaneous infusion. The results will be compared with each other.

Placebo

Sodium chloride 0.9% administered as a subcutaneous infusion via syringe driver for 48 hours.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ketamine

Patients will receive either ketamine as subcutaneous infusion or placebo as subcutaneous infusion. The results will be compared with each other.

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Ketalar Sodium chloride 0.9%

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Age 18-70 years. In-patient. Cancer pain judged to have a neuropathic component. Clinically normal renal and hepatic function. Able to cooperate and understand information. Worst pain at rest or on movement 5 or more (NRS 0-10). Pain currently treated with continuous subcutaneous morphine infusion. The daily morphine dose is 48mg or more per 24 hours and a 30% increase in the daily dose has not provided sufficient pain relief.

Not treated with ketamine during the last 48 hours prior to inclusion.

\-

Exclusion Criteria

Reduced renal or hepatic function. Suspicion of morphine toxicity (sedation, hallucination, myoclonus, increasing pain).

Increased intracranial pressure (suspicion of cerebral metastases) or cerebral metastases.

Unable to cooperate/ understand information. Worst pain at rest or on movement less than 5 on NRS. Current treatment with other opioids than morphine. The patient is undergoing radiotherapy in the pain area, or has received radiotherapy in the pain area within the last four weeks.

Changes in the use of analgesics (paracetamol, NSAIDS), adjuvant drugs (antidepressants, antiepileptic, corticosteroids, muscle relaxants) or their dosages less than 2 days prior to inclusion or during the study period.

Pregnant and lactating women. Any situation in which an increase in blood pressure would constitute a hazard. Acute intermittent porphyria. Psychiatric illness, epilepsy, alcoholism, glaucoma. Hypersensitivity to any of the drugs ingredients. Current treatment with ketamine.

\-
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Haukeland University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Rae F Bell, M.D. PhD.

Role: PRINCIPAL_INVESTIGATOR

Pain Clinic, Haukeland University Hospital, 5021 Bergen, Norway

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Haukeland University Hospital

Bergen, Hordaland, Norway

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Norway

References

Explore related publications, articles, or registry entries linked to this study.

Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain. 1995 Sep;62(3):259-274. doi: 10.1016/0304-3959(95)00073-2.

Reference Type BACKGROUND
PMID: 8657426 (View on PubMed)

Ko SW, Wu LJ, Shum F, Quan J, Zhuo M. Cingulate NMDA NR2B receptors contribute to morphine-induced analgesic tolerance. Mol Brain. 2008 Jun 17;1:2. doi: 10.1186/1756-6606-1-2.

Reference Type BACKGROUND
PMID: 18803856 (View on PubMed)

Mayer DJ, Mao J, Price DD. The association of neuropathic pain, morphine tolerance and dependence, and the translocation of protein kinase C. NIDA Res Monogr. 1995;147:269-98.

Reference Type BACKGROUND
PMID: 8742791 (View on PubMed)

Qi X, Evans AM, Wang J, Miners JO, Upton RN, Milne RW. Inhibition of morphine metabolism by ketamine. Drug Metab Dispos. 2010 May;38(5):728-31. doi: 10.1124/dmd.109.030957. Epub 2010 Feb 2.

Reference Type BACKGROUND
PMID: 20124399 (View on PubMed)

Bell RF, Eccleston C, Kalso E. Ketamine as adjuvant to opioids for cancer pain. A qualitative systematic review. J Pain Symptom Manage. 2003 Sep;26(3):867-75. doi: 10.1016/s0885-3924(03)00311-7.

Reference Type BACKGROUND
PMID: 12967737 (View on PubMed)

Bell RF. Low-dose subcutaneous ketamine infusion and morphine tolerance. Pain. 1999 Oct;83(1):101-3. doi: 10.1016/s0304-3959(99)00096-2.

Reference Type BACKGROUND
PMID: 10506678 (View on PubMed)

Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006 Oct;22(10):1911-20. doi: 10.1185/030079906X132488.

Reference Type BACKGROUND
PMID: 17022849 (View on PubMed)

Hagelberg NM, Peltoniemi MA, Saari TI, Kurkinen KJ, Laine K, Neuvonen PJ, Olkkola KT. Clarithromycin, a potent inhibitor of CYP3A, greatly increases exposure to oral S-ketamine. Eur J Pain. 2010 Jul;14(6):625-9. doi: 10.1016/j.ejpain.2009.10.003. Epub 2009 Nov 7.

Reference Type BACKGROUND
PMID: 19897389 (View on PubMed)

Nisbet AT, Mooney-Cotter F. Comparison of selected sedation scales for reporting opioid-induced sedation assessment. Pain Manag Nurs. 2009 Sep;10(3):154-64. doi: 10.1016/j.pmn.2009.03.001.

Reference Type BACKGROUND
PMID: 19706353 (View on PubMed)

Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

Reference Type BACKGROUND
PMID: 2748771 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2012/539

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.