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

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

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]

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Muscle Cramps
• Intervention / Treatment: Drug: orphenadrine; Drug: Placebo

Detailed Description

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]

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sherief M Abd-Elsalam, lecturer; Phone Number: 002 01000058842; Email: Sherif_tropical@yahoo.com

Study Locations

• Egypt
  • Tanta, Egypt
    • Recruiting
    • Tanta University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sherief Abd-Elsalam
• Collaborators: Tanta University
• Investigators: Principal Investigator: Asem A Elfert, Professor, TUH; Study Chair: Samah Mosaad, Lecturer, TUH; Study Chair: Lobna Aboaly, Professor, TUH; Study Chair: Walaa ElKhalawany, Lecturer, TUH; Study Director: Sherief Abd-Elsalam, Lecturer, TUH

Publications and helpful links

General Publications

• Abd-Elsalam S, Ebrahim S, Soliman S, Alkhalawany W, Elfert A, Hawash N, Elkadeem M, Badawi R. Orphenadrine in treatment of muscle cramps in cirrhotic patients: a randomized study. Eur J Gastroenterol Hepatol. 2020 Aug;32(8):1042-1045. doi: 10.1097/MEG.0000000000001622.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2028
• Study Completion (Anticipated): December 1, 2028

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: April 21, 2015
• First Posted (Estimate): April 22, 2015

Study Record Updates

• Last Update Posted (Actual): June 7, 2019
• Last Update Submitted That Met QC Criteria: June 6, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Liver Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Fibrosis; Liver Cirrhosis; Spasm; Muscle Cramp; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Neuromuscular Agents; Muscle Relaxants, Central; Antiparkinson Agents; Anti-Dyskinesia Agents; Cytochrome P-450 CYP2B6 Inhibitors; Orphenadrine
• Other Study ID Numbers: muscle cramps in cirrhotics

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No