NCT02256956

Brief Summary

Low dose tricyclic antidepressant drugs are routinely administered co-analgesics in pain medicine. Amitriptyline is largely considered as a gold standard. Amitriptyline underlies cytochrome CYP2D6 and CYP2D19 metabolism. CYP2D6 is highly polymorphic; numerous genetic variants result in 4 major classes characterizing enzymatic activity: poor metabolizers, intermediate metabolizers, extensive metabolizers and ultrarapid metabolizers. It is not known to which extent metabolizer classes determine pain outcomes or side-effects. As only one in three pain patients is considered to be a responder to amitriptyline's co-analgesic effect, prediction of treatment efficacy with a fast and easy to perform bedside test may contribute to the patients quality of life. The aim of this study is to determine the influence of cytochrome variants on experimental pain, drug related side-effects and finally identification of active metabolites.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for phase_4 chronic-pain

Timeline
Completed

Started Nov 2014

Longer than P75 for phase_4 chronic-pain

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 29, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 6, 2014

Completed
26 days until next milestone

Study Start

First participant enrolled

November 1, 2014

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2018

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2019

Completed
Last Updated

January 24, 2019

Status Verified

January 1, 2019

Enrollment Period

3.5 years

First QC Date

September 29, 2014

Last Update Submit

January 23, 2019

Conditions

Chronic Pain

Keywords

Pharmacogenetics of Amitriptyline

Outcome Measures

Primary Outcomes (1)

  • Nociceptive withdrawal reflex

    Measure of involuntary electromyographic amplitude

    During measurement, expected to be ca. 2-3 minutes

Secondary Outcomes (2)

  • Pharmacogenetic information on CYP2D6 metabolism

    At baseline, i.e. on day 1

  • Changes in plasmatic metabolite level

    Throughout study duration, expected to be ca. 20 days

Study Arms (2)

Amitriptyline first, Placebo second

ACTIVE COMPARATOR

Amitriptyline first, Placebo second

Drug: AmitriptylineDrug: Tolterodine

Placebo first, Amitriptyline second

ACTIVE COMPARATOR

Placebo first, Amitriptyline second

Drug: AmitriptylineDrug: Tolterodine

Interventions

AmitriptylineDRUG

25 mg / day for 10 days

Also known as: Tryptizol
Amitriptyline first, Placebo secondPlacebo first, Amitriptyline second
TolterodineDRUG

Placebo 1 mg / day for 10 days

Amitriptyline first, Placebo secondPlacebo first, Amitriptyline second

Eligibility Criteria

Age18 Years - 65 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy
  • Male
  • \>7 Metabolic Equivalents
  • Written informed consent

You may not qualify if:

  • Chronic pain syndrome
  • Drug abuse
  • Alcohol abuse
  • Suspicion of neurologic dysfunction at tested sites
  • Ongoing treatment with antidepressants
  • Ongoing treatment with analgesics
  • Pretreatment with any CYP3A inducers or inhibitors
  • Known allergy to tested drugs
  • Elevated eye pressure
  • Obstructive uropathy
  • Heart disease
  • Pulmonary disease
  • Neurological disease
  • Psychiatric illness

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dep. of Anesthesiology, Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (1)

  • Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. J Clin Pharmacol. 2012 Jan;52(1):6-17. doi: 10.1177/0091270010394852. Epub 2011 Mar 17.

    PMID: 21415285BACKGROUND

MeSH Terms

Conditions

Chronic Pain

Interventions

AmitriptylineTolterodine Tartrate

Condition Hierarchy (Ancestors)

PainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsPhenylpropanolaminePropanolaminesAmino AlcoholsAlcoholsPropanolsAminesBenzhydryl CompoundsBenzene DerivativesCresolsPhenols

Study Officials

  • Ulrike Stamer, Professor

    Bern University Hospital

    STUDY CHAIR

  • Pascal H Vuilleumier, MD

    Bern University Hospital

    PRINCIPAL INVESTIGATOR

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
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 29, 2014

First Posted

October 6, 2014

Study Start

November 1, 2014

Primary Completion

May 1, 2018

Study Completion

January 1, 2019

Last Updated

January 24, 2019

Record last verified: 2019-01

Locations

CH(1)