Efficacy Study of Nabilone in the Treatment of Diabetic Peripheral Neuropathic Pain

NCT01035281 | Unknown Phase 3 DMC

• 1 other identifier: U Calgary # UCNABDPN01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathic pain occurs as a result of damage or disease of the peripheral or central nervous system. Regardless of its cause, neuropathic pain (NeP) leads to a characteristic clinical picture characterized by ongoing pain with steady or dysesthetic pain, such as burning or aching, and paroxysmal pain such as shooting or stabbing. In conditions such as diabetic neuropathy, changes in the membrane-bound proteins that form ion channels may alter the electrical properties of the injured neuron, called remodeling. The net effect of membrane remodeling is greater excitability of neurons, leading to a tendency towards action potential generation and propagation in injured primary sensory neurons which occurs in the context of nerve injury and disease. Over the past decade, a new endogenous cannabinoid receptor-mediated system within the nervous system and upon immune-mediated cells has been described. The cannabinoid receptor system consists of two receptors, CB1 and CB2 receptors, as well as endogenously produced endocannabinoids which agonize these receptors. This is a multicenter trial amongst Western Canadian sites to compare the efficacy of nabilone versus placebo in treating patients with chronic neuropathic pain (NeP) due to diabetic peripheral neuropathy (DPN). A one-week screening period will occur, during which pain scores and sleep scores will be tabulated. Following screening, a 4-week period of single blind treatment with flexible dosing of nabilone at 0.5 - 4 mg/day will initiate. All subjects will begin with nabilone therapy of 1 mg daily for a minimum of 4 days, with the dose of the study medication assessed and adjusted either upwards or downwards as needed to balance efficacy for pain control with tolerability of possible side effects. All subjects who experience at least a 30% reduction in their weekly mean pain score during the single blind flexible dosing phase will be considered a responder, and will be further continued in the study. During the double-blind portion of the study, subjects randomized to nabilone will continue on the dose of nabilone achieved at the completion of the single-blind phase, and this dose will be maintained throughout the double-blind phase. Subjects randomized to placebo will receive 1 mg of nabilone daily for one week, followed by 4 consecutive weeks of placebo. This dose of nabilone will permit a tapering for those subjects achieving a higher daily dose of nabilone during the single-blind phase, or will maintain those who were taking only 1 mg per day in the single-blind phase, preventing an abrupt termination of treatment in subjects who are randomized into the placebo portion of the study.

Conditions

Diabetic Neuropathies

Keywords

Diabetic Neuropathies; Neuropathic Pain; Cannabinoids; Tree Number C10.668.829.300

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy of nabilone compared to placebo in the treatment of diabetic neuropathy-associated peripheral neuropathic pain (DPN).

  2008 - 2012

Secondary Outcomes (1)

• To evaluate safety and tolerability of nabilone for the treatment of neuropathic pain in subjects with diabetic peripheral neuropathy.

  2008 - 2012

Study Arms (2)

Nabilone

EXPERIMENTAL

A one-week screening period will occur, during which pain scores and sleep scores will be tabulated. Following screening, a 4-week period of single blind treatment with flexible dosing of nabilone at 0.5 - 4 mg/day will initiate.

Drug: Nabilone, flexible dosing

Placebo

PLACEBO COMPARATOR

All subjects who experience at least a 30% reduction in their weekly mean pain score during the single blind flexible dosing phase will be considered a responder, and will be further continued in the study. During the double-blind portion of the study, subjects randomized to nabilone will continue on the dose of nabilone achieved at the completion of the single-blind phase, and this dose will be maintained throughout the double-blind phase. Subjects randomized to placebo will receive 1 mg of nabilone daily for one week, followed by 4 consecutive weeks of placebo. This dose of nabilone will permit a tapering for those subjects achieving a higher daily dose of nabilone during the single-blind phase, or will maintain those who were taking only 1 mg per day in the single-blind phase, preventing an abrupt termination of treatment in subjects who are randomized into the placebo portion.

Drug: Nabilone, flexible dosing

Interventions

Nabilone, flexible dosing DRUG

nabilone at 0.5 - 4 mg/day

Also known as: Cesamet

Nabilone; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, ages between 18-80 years;
• Signed and dated informed consent;
• Females of childbearing potential must have a negative serum β-HCG pregnancy test and be practicing an effective form of contraception (accepted methods are hormonal \[oral contraceptive or injectable contraceptive\], double barrier with spermicide, or intrauterine device-IUD). Complete abstinence may be considered acceptable, but must be determined on a case-by-case basis with the clinical investigator.
• Diagnosis of DPN-associated NeP syndrome, confirmed by a qualified Neurologist or pain specialist, with persistence for a minimum of 3 months.
• Score of ≥4 on the DN4 questionnaire, a single page survey consisting of historical questions and one examination portion using light touch and pinprick over the region of suspected neuropathic pain. This has high sensitivity and specificity for neuropathic pain.
• Must complete ≥4 daily pain diaries during the week of the screening phase prior to randomization;
• Must have a daily mean pain score of ≥4 over the screening period prior to randomization based on Daily Pain Rating Scale (DPRS);
• Must have a score of \>40 mm on the visual analog scale (VAS) of the Short Form McGill Pain Questionnaire (SF-MPQ);
• Screening laboratory values must be within normal limits, or abnormalities must be deemed clinically insignificant in the judgment of the investigator
• Subject must be deemed capable of complying with study schedule, procedures and medications.

You may not qualify if:

• Pregnant or lactating women or women of childbearing potential not using acceptable method of contraception;
• Subjects with neuropathic pain that is not due to DPN
• Any skin conditions in the affected areas with NeP that (in the judgment of the investigator) could interfere with evaluation of the NeP
• Current or past DSM-IV-TRTM (2000) diagnosis of schizophrenia, psychotic disorder, bipolar affective disorder or obsessive-compulsive disorder and Major Depressive Disorder (MDD);
• Current or past DSM-IV-TRTM (2000) diagnosis of substance abuse or dependence within the last 6 month;
• Use of marijuana or other cannabinoids during the study. Discontinuation of these substances 30 days prior to the screening visit is permitted. The study consent must be signed and dated prior to the discontinuation of these substances;
• Clinically significant or unstable conditions that, in the opinion of the investigator, would compromise participation in the study. This includes, for example, medical conditions such as, but not limited to: hepatic, renal, respiratory, hematological, immunologic, or cardiovascular diseases (eg, myocardial infarction within previous month, ventricular arrhythmia recent severe heart insufficiency), inflammatory or rheumatologic disease, active infections, symptomatic peripheral vascular disease, and untreated endocrine disorders;
• History of seizure disorder, except febrile seizures of childhood;
• A glycated hemoglobin (HbA1C) of more than 11% at screening
• Any other condition, which in the investigator's judgment might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study. This includes any condition precluding nabilone use;
• Malignancy within past 2 years with exception of basal cell carcinoma;
• Urine screen positive for illicit substances, including tetrahydrocannaboids (THC) such as marijuana at screening (Visit 1);
• Liver function tests or liver enzymes \>3 times the upper limit of normal (ULN)
• Other blood or urine laboratory results which are sufficiently abnormal in the view of the investigator(s) to raise concern about the enrollment of this subject in this study.
• A previous history of intolerance or hypersensitivity to cannabinoids or other medications or substances with similar chemical structure;

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Hotchkiss Brain Institute

Calgary, Alberta, T2N4N1, Canada

RECRUITING

MeSH Terms

Conditions

Diabetic Neuropathies; Neuralgia

Interventions

nabilone

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Cory Toth, MD

  U of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shefina Mawani, BScN

CONTACT

4032203659; shefina.mawani@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 18, 2009
• Study Start: January 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: April 1, 2011
• Last Updated: December 18, 2009

Record last verified: 2009-12

Locations

CA (1)