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

Sherief Abd-Elsalam

Status and phase: Enrolling; Phase 3

Conditions: Muscle Cramps; Liver Cirrhosis

Treatments: Drug: Placebo; Drug: orphenadrine

Study type: Interventional

Funder types: Other

Identifiers

NCT02423395

muscle cramps in cirrhotics

Details and patient eligibility

About

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]

Full 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]

Enrollment: 100 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

100 participants in 2 patient groups, including a placebo group

Orphenadrine(Norflex)

Experimental group

Description:

50 patients will be treated with orphenadrine 100 mg twice daily for 1 month

Treatment:

Drug: orphenadrine

Placebo

Placebo Comparator group

Description:

50 patients will be given placebo

Treatment:

Drug: Placebo