Study of Orphenadrine' in the Treatment of Muscle Cramps in Patients With Cirrhosis

Study Overview
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Brief Summary
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Muscle cramps are common in patients with liver disease and associated with significantly diminished quality of life. Patients with cirrhosis often experience muscle cramps with varied frequency and severity. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes (1) Orphenadrine is an anticholinergic drug with prominent central nervous system (CNS) and peripheral actions used to treat painful muscle spasms and other similar conditions. The combination of anticholinergic effects and CNS penetration make orphenadrine useful for pain of all etiologies, including from: radiculopathy, muscles, and headaches. [3,4]

Detailed Description
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Muscle cramps are common in patients with liver disease and associated with significantly diminished quality of life. Patients with cirrhosis often experience muscle cramps with varied frequency and severity. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes [1]. Although a number of mechanisms for cramps in liver disease have been postulated and have been targeted by medical therapies, a clear picture of the causal events has not emerged. Several agents as vitamin E, human albumin, zinc, taurine, eperisone hydrochloride and branched-chain amino acids have shown some benefit in small uncontrolled studies, although large randomized controlled trials are lacking [2]. Orphenadrine is an anticholinergic drug with prominent central nervous system (CNS) and peripheral actions used to treat painful muscle spasms and other similar conditions. The combination of anticholinergic effects and CNS penetration make orphenadrine useful for pain of all etiologies, including from: radiculopathy, muscles, and headaches. [3,4] Orphenadrine is structurally related to diphenhydramine and carries relatively stronger anticholinergic and weaker sedative properties, It is mostly excreted through the kidneys.[5]

Official Title
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Randomized Study of Orphenadrine' in the Treatment of Muscle Cramps in Patients With Cirrhosis

Conditions
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Liver Cirrhosis, Muscle Cramps

Intervention / Treatment
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* Drug: orphenadrine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhosis Muscle cramps( ≥3 cramps per week ) Exclusion Criteria: • Allergy to orphenadrine Renal impairment Pregnant and lactating women Peripheral vascular disease Peripheral neuropathy Medications as calcium channel blockers, conjugated estrogens and naproxen. Glaucoma Prostatic enlargement
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orphenadrine(Norflex)<br>50 patients will be treated with orphenadrine 100 mg twice daily for 1 month | Drug: orphenadrine<br>* Orphenadrine in muscle cramps in cirrhotic patients<br>* Other names: Norflex;|
| Placebo Comparator: Placebo<br>50 patients will be given placebo | Drug: Placebo<br>* calcium in muscle cramps in cirrhotic patients<br>* Other names: calcium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of muscle cramps | questionnaire | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life of these patients | questionnaire | 3 months |