Protocol Number: 01-D-0076

Title:

Morphine, Nortriptyline and Their Combination in Sciatica Treatment

Number:

01-D-0076

Summary:

This study will test the effectiveness of two drugs-nortriptyline and MS Contin (a type of morphine)-to treat pain caused by lumbar radiculopathy, or sciatica. Sciatica results from damage to the lumbar nerve roots, typically causing back pain and sharp, shooting pain down one or both legs. Although sciatica is common, there are no good treatments for it. Tricyclic antidepressants, such as nortriptyline, and opioids, such as morphine, have been effective in treating other kinds of pain from nerve damage.

Patients between 18 and 65 years of age who have had sciatica pain daily for at least 3 months may be eligible for this study.

Participants will provide a medical history and occupational and other social information. They will undergo a neurological examination, routine blood tests and an electrocardiogram and will fill out three questionnaires providing information on daily functioning and psychological well-being.

This "cross-over" study consists of several parts, including a baseline study and four different treatment regimens. During each part, patients keep a daily log in which they rate their pain, record other procedures they undergo, such as injections and manipulations, and record medication side effects.

In the first week of the study, patients remain on their current medications. Any antidepressants or opioids are stopped gradually before starting the drug trials. After the first week, patients go through the following four drug trials in random order:

1. Nortriptyline and inert placebo-Patients take nortriptyline in doses ranging from 25 mg. to 100 mg. and an inert placebo for morphine. (An inert placebo is a dummy pill; it looks like the test drug but has no active ingredient.)

2. MS Contin (morphine) and inert placebo-Patients take MS Contin in doses ranging from 30 mg. to 90 mg. and an inert placebo for nortriptyline.

3. Nortriptyline and MS Contin-Patients take MS Contin and nortriptyline in the same dose ranges as for each drug alone.

4. Active placebo and inactive placebo-Patients take an active placebo-in this case benztropine-and an inert placebo. An active placebo is a drug that does not work for the problem being studied but whose side effects are like those of the test drug-in this case, slight sleepiness or dry mouth. Benztropine is given at one-third the recommended dosage.

For each drug regimen, the medication dose is increased gradually over 5 weeks until the maximum tolerated dose is reached. At the end of each regimen, patients are taken off the study drugs over a 12-day tapering period and are off drugs completely for another 2 days.

Patients are seen by a doctor or nurse at the 7-week point in each study period. After all the drug trials are finished, patients repeat the questionnaires they filled out at the beginning of the study. Patients and their doctors will be informed of the medications that were effective in each individual's care.

Sponsoring Institute:

National Institute of Dental And Craniofacial Research (NIDCR)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

In this study chronic lumbar radicular signs and symptoms are defined as pain located in the lower lumbar spine corresponding to L1 and below for at least 3 months with radicular characteristics, i.e. pain described as sharp, burning, with numbness and/or tingling.

Ability to understand the study measures and mentally capable of give consent to participate in the study (based on an 8th grade education level)

Willingness to refrain from taking opioids other than their study medication.

Patients with failed back syndrome who satisfy the criteria outlined in Appendix II.

Patients with a pain level of 4/10 or greater on a scale of 0 to 10.

EXCLUSION CRITERIA:

Major coexisting medical condition such as cancer, chronic obstructive pulmonary disease and severe hepatic and renal dysfunction.

Prostatic disease requiring usage of urological medications.

Pregnancy or lactation.

Unwillingness to discontinue pain medication(s) at study onset as follows: narcotic pain medications, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs).

Presence of pain of greater intensity in any other location than the low back or leg.

Current major depression requiring usage of antidepressants.

History of narcotic abuse at any time in the past and/or drug or alcohol abuse in the past year.

History of narrow angle glaucoma.

History of epilepsy.

Current symptoms of coronary artery disease.

History of fibromyalgia as described by Wolfe F et al., (1990) (a minimum of 12 out of 19 points of tenderness must be present to satisfy criteria for fibromyalgia).

History of spinal unstability (based on an MRI finding of grade II spondylolisthesis or greater).

Cognitive impairment such that the individual is unable to give informed consent, complete study data collection tools or required study visits.

Unwillingness to use adequate contraception (such as birth control pills or barrier methods with spermicide simultaneously).

Presence of other medical condition presenting with numbness and pain in lower extremities, such as diabetic polyneuropathy and peripheral vascular disease.

Allergy to any of the medications used in the study.

Age 18 years or less due to rarity of sciatica in this age group.

Special Instructions: Currently Not Provided

Keywords:

Low Back Pain

Opioid

Antidepressant

Randomized Controlled Trial

Analgesic

Recruitment Keywords:

Low Back Pain

Sciatica

Conditions:

Radiculopathy

Sciatica

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Controlled trial of imipramine for chronic low back pain

Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity

Are opioids effective in relieving neuropathic pain

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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