Imipramine Treatment for Patients With Multi-organ Bodily Distress Syndrome (Stress-3)

Tracking Information
First Submitted Date ICMJE	January 13, 2012
First Posted Date ICMJE	January 26, 2012
Last Update Posted Date	May 9, 2017
Study Start Date ICMJE	January 2012
Actual Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 11, 2013)	Global Clinical Improvement Scale [ Time Frame: After 13 weeks ]; Questionnaire, patient-rated improvement of health since the beginning of the study.
Original Primary Outcome Measures ICMJE; (submitted: January 25, 2012)	Global Clinical Improvement Scale [ Time Frame: After 13 weeks ]; Questionaire, patient-rated improvement of health since the begining of the study.
Change History	Complete list of historical versions of study NCT01518634 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 11, 2013)	SF-36 [ Time Frame: At 1 and 13 weeks ]Questionnaire, patient-rated. Assessment of physical, social and mental functioning; Visual Analogue Scale for pain and worst symptom [ Time Frame: At 1 and 13 weeks ]; Symptom Checklist (SCL) [ Time Frame: At 1, 3 and 13 weeks ]; Functional Illness Checklist (FIC) [ Time Frame: At 1, 3 and 13 weeks ]; WHODAS II [ Time Frame: At 1 and 13 weeks ]
Original Secondary Outcome Measures ICMJE; (submitted: January 25, 2012)	SF-36 [ Time Frame: At 1 and 13 weeks ]Questionair, patient-rated. Assessment of physical, social and mental funtioning; Visual Analogue Scale for pain and worst symptom [ Time Frame: At 1 and 13 weeks ]; Symptom Checklist (SCL) [ Time Frame: At 1, 3 and 13 weeks ]; Functional Illness Checklist (FIC) [ Time Frame: At 1, 3 and 13 weeks ]; WHODAS II [ Time Frame: At 1 and 13 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Imipramine Treatment for Patients With Multi-organ Bodily Distress Syndrome
Official Title ICMJE	Treatment of Multi-organ Bodily Distress Syndrome. A Double-blinded Placebo Controlled Trial of the Effects of Imipramine (Stress-3)
Brief Summary	The aim of this study is to test the effect of the tricyclic antidepressant Imipramine in patients with longlasting health problems with no known medical explanation, defined as multi-organ Bodily distress syndrome (BDS). Pharmacological treatment of patients with BDS have never been tested, and Imipramine i low dosage (10-75 mg) has the potential of reducing both pain and other symptoms of bodily distress for patients with BDS. Control conditions are pill placebo. Study duration is 19 weeks for each of the 140 patients. End point is 13 weeks, i.e. after 10 weeks of 25-75 mg study drug.
Detailed Description	The aim of this study is to test the effect of Imipramine in patients with multi-organ Bodily distress syndrome (BDS). BDS is a unifying diagnosis that encompasses a group of closely related conditions such as somatization disorder, fibromyalgia, irritable bowel syndrome and chronic fatigue syndrome. The project consists of a double-blinded placebo controlled trial of treatment with the tricyclic antidepressant Imipramine in dosages of 25-75 mg. Primary outcome is patient-rated improvement measured by Clinical Global Improvement Scale (CGI-I). Secondary outcome is functional level (physical, mental and social) measured by the SF-36 Physical Component Summary (PCS). The study requires 140 participants and study duration is 19 weeks for each patient. End point is 13 weeks, i.e. after 10 weeks of 25-75 mg study drug.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Somatisation Disorder; Somatoform Disorders
Intervention ICMJE	Drug: Imipramine treatment Two-week of wash-out, one week of 10 mg study drug, 10 weeks of 25-75 mg study drug, four weeks of phasing-out and finaly two weeks after ther last dose of study drug to monito adverse events.; Drug: Placebo Two-week of wash-out, one week of 10 mg study drug, 10 weeks of 25-75 mg study drug, four weeks of phasing-out and finaly two weeks after ther last dose of study drug to monito adverse events.
Study Arms	Experimental: Imipramine treatment Intervention: Drug: Imipramine treatment; Placebo Comparator: Placebo Intervention: Drug: Placebo
Publications *	Agger JL, Schröder A, Gormsen LK, Jensen JS, Jensen TS, Fink PK. Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study. Lancet Psychiatry. 2017 May;4(5):378-388. doi: 10.1016/S2215-0366(17)30126-8. Epub 2017 Apr 10.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 13, 2017)	138
Original Estimated Enrollment ICMJE; (submitted: January 25, 2012)	140
Actual Study Completion Date	December 2016
Actual Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: First time refered patients fulfilling diagnostic criteria for BDS multi-organ type with symptoms for more than 3 of 4 symptom categories; Moderate or severe impact on daily life; Symptoms lasting for at least 2 years; Age 20-50 years; Born in Denmark or have Danish parents. The patient understands, speaks, writes and read Danish. Exclusion Criteria: Presence og other physical of psychiatric condition, if the symptoms of this condition can not clearly be separated from symptoms of BDS; Current moderate or severe depression, patients in continuous antidepressant treatment because of moderate or severe depression, and patients with other severe psychiatric disorder that demands treatment, or if the patient is suicidal.; A lifetime-diagnosis of psychoses, mania or depression with psychotic symptoms (ICD-10: F20-29, F30-31, F32.3, F33.3); Abuse of alcohol, narcotics or drugs; Pregnancy, breastfeeding or current pregnancy wish. Fertile women must use effective anticonception, (hormonal contraception, contraceptive injection, implant or patches, intrauterine system and device, vaginal ring).; Treatment with all pain modulating drugs, e.g. all analgesics, antidepressants, antiepileptica and other types of medication with pain relieving properties must be discontinued at least two weeks before the treatment phase.; Imipramine treatment in sufficient dosage within the last year, i.e. 25 mg daily continuously for at least 8 weeks.; Allergy to study medication or excipients in study medication.; Patients with previous med myocardial infarction, congestive heart failure, signs of conduction defects or abnormalities on ECG (first degree AV-block, bundle branch block or prolonged QT-interval), narrow-angle glaucoma, porphyria, inherited galactose intolerance, epilepsy, hepatic insufficiency and severe renal impairment; Simultaneous use of: antipsychotics oral anticoagulants diuretics sympathomimetics and CNS-stimulating drugs (amphetamine-like drugs) all serotonergic drugs, e.g. SSRI, SNRI and TCA, the dietary supplement hypericum perforatum, non-selective, irreversible or selective, reversible monoamine oxidase (MAO) inhibitors, triptans, tramadol, pethidin and tryptophan the drugs cimetidine (H2-antagonist), quinidine (antiarrythmics), clonidine (antihypertensive), fluconazol (antimycotics), clindamycin, clarithromycin, erythromycin (antibiotics), droperidol (anaesthetic), levodopa (antiparkinson), mefloquine (antimalaria), phenytoin, barbiturates, carbamazepin (antiepileptica) Bupropion (tobacco dependence), celecoxib (NSAID), cinacalcet (antiparathyroid drug), duloxetine (SNRI), flufenazin (antipsychotic), fluoxetin (SSRI), gefitinib (antineoplastic), moclobemid (MAO), paroxetine, Sertraline (SSRI), Terbinafine (antimycotics), Yohimbin (erectile dysfunction) samt fluvoxamin (SSRI), ciprofloxacin and enoxacin (microbiotic), because plasma concentration of Imipramine can increase with the simultaneous use of these potent CYP2D6- and CYP1A2- inhibitors
Sex/Gender	Sexes Eligible for Study: All
Ages	20 Years to 50 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Denmark
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01518634
Other Study ID Numbers ICMJE	2011-004294-87
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University of Aarhus
Study Sponsor ICMJE	University of Aarhus
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Per k Fink, dr.med Research Clinic for Functional Disorders, Aarhus University Hospital
PRS Account	University of Aarhus
Verification Date	June 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP