Imipramine and Pregabalin Combination in Painful Polyneuropathy

NCT01047488 | Unknown Phase 4 DMC

• 2 other identifiers: tcapgbcomb12009-013642-80
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief Summary

Polyneuropathy of different etiologies is often associated with pain and the standard treatment for this type of pain is gabapentinoids or antidepressants. The hypothesis of this study is that the combination of the gabapentinoid pregabalin and the antidepressant imipramine will provide better pain relief than the single compounds alone. This is a randomized, placebo-controlled, double-blind, 4-way, cross-over trial of pregabalin 300 mg/day, imipramine 75 mg/day and their combination versus placebo. The study will include 60 patients and the treatment outcome will be pain intensity as measured by numeric rating scales.

Conditions

Polyneuropathy

Keywords

polyneuropathy; neuropathic pain; treatment

Outcome Measures

Primary Outcomes (1)

• Total pain intensity as measured by numeric rating scale 0-10 points.

  Median of ratings from last week of each treatment period

Secondary Outcomes (7)

• Verbal pain relief scale with 6 classes

  End of each treatment period

• Specific pain symptom rated by numeric rating scales 0-10 points

  Median of ratings from last week of each treatment period

• Rating of evoked pains symptoms (pressure, brush, repetitive pin-prick, cold) as measured by numeric rating scales 0-10 points

  End of each treatment period

• Sleep disturbance as measured by numeric rating scale 0-10 points

  Median of ratings from last week of each treatment period

• Consumption of escape medication (number of tablets of paracetamol)

  Total consumption during last week of each treatment period

Study Arms (4)

Imipramine

ACTIVE COMPARATOR

Imipramine tablets and placebo capsules to pregabalin

Drug: Imipramine

Pregabalin

ACTIVE COMPARATOR

Pregabalin capsules and placebo tablets to imipramine

Drug: Pregabalin

Imipramine plus pregabalin

EXPERIMENTAL

Imipramine tablets and pregabalin capsules

Drug: Imipramine, pregabalin

Placebo

PLACEBO COMPARATOR

Placebo tablets to imipramine and placebo capsules to pregabalin

Drug: Placebo

Interventions

Imipramine DRUG

Tablet 25 mg, 3 tablets evening (extensive metabolizers) or 1 tablet evening (poor metabolizers), daily, 5 weeks

Also known as: Imipramin DAK

Imipramine

Pregabalin DRUG

Capsule 75 mg, 2 capsules twice daily, daily, 5 weeks

Also known as: Lyrica

Pregabalin

Imipramine, pregabalin DRUG

Imipramine: tablet 25 mg, 3 tablets evening (extensive metabolizers) or 1 tablet evening (poor metabolizers), daily, 5 weeks Pregabalin: capsule 75 mg, 2 capsules twice daily, daily, 5 weeks

Also known as: Imipramin DAK, Lyrica

Imipramine plus pregabalin

Placebo DRUG

Placebo tablets to imipramine 25 mg, 3 or 1 tablet evening, daily, 5 weeks Placebo capsules to pregabalin 75 mg, 2 capsules daily, daily, 5 weeks

Placebo

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 20 - 85 years.
• Characteristic symptoms of polyneuropathy for at least 6 months.
• Polyneuropathy diagnosis confirmed by typical clinical signs (distal sensory disturbance/lack of distal deep tendon reflexes) and/or electrophysiological tests and/or abnormal quantitative sensory tests.
• Total pain intensity rating of at least 4 on a 0-10 points numeric rating scale.
• Pain present at least 4 days a week.
• For diabetics: diabetes diagnosis for at least 6 months and stable metabolic control for at least 3 months.
• For other secondary polyneuropathies: stable for at least 6 months.
• For fertile females: adequate anticonceptive treatment.
• Written informed consent.

You may not qualify if:

• Other cause of pain.
• Contraindications against imipramine.
• Allergic reactions towards imipramine or pregabalin.
• Known adverse reactions during imipramine or pregabalin treatment.
• Pregnancy.
• Severe systemic disease.
• Ongoing treatment with antidepressants, antipsychotics, anticonvulsants, opioids, propranolol, kinidine, monoamine oxidase inhibitor.
• Inability to follow study protocol.

Sponsors & Collaborators

• Odense University Hospital: lead
• Pfizer: collaborator
• Nycomed: collaborator

Study Sites (3)

Department of Neurology, Aalborg Hospital

Aalborg, DK-9000, Denmark

Location

Department of Neurology, Aarhus University Hospital

Aarhus, DK-8000, Denmark

Location

Department of Neurology, Odense University Hospital

Odense, DK-5000, Denmark

Location

MeSH Terms

Conditions

Polyneuropathies; Neuralgia

Interventions

Imipramine; Pregabalin

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Søren H. Sindrup, MD

  Department of Neurology, Odense University Hospital

  STUDY CHAIR

• Jakob V. Holbech, MD

  Department of Neurology, Odense University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Søren H. Sindrup, MD

CONTACT

+45 65412471; soeren.sindrup@ouh.regionsyddanmark.dk

Jakob V. Holbech, MD

CONTACT

Holbech@dadlnet.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: January 13, 2010

Record last verified: 2010-01

Locations

DK (3)