Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00150839
Status:
COMPLETED
Last Update Posted:
2020-12-14
First Post:
2005-09-06
Brief Title:
Hippocampal Volume in Young Patients With Major Depression Before and After Combined Antidepressive Therapy
Sponsor:
University of Erlangen-Nürnberg Medical School
Organization:
University of Erlangen-Nürnberg Medical School
Study Overview
Official Title:
Hippocampal Volume in Young Patients With Major Depression Before and After Combined Antidepressive Therapy - a Monocentric Double-blind Placebo-controlled Trial
Status:
COMPLETED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COATS
Brief Summary:
The proposed study is a randomized placebo-controlled double-blind trial to evaluate the safety and efficacy of antidepressant combination for the treatment of depression
Depressive disorder is one of the most common human diseases with a high burden for every patient herhis family health care system and society as a whole Actual treatment concepts of depressive disorders include pharmacologic biologic eg electroconvulsive therapy light therapy and psychologic therapy Even though effective therapeutic options are at hand therapy needs time It is often not possible to reach full remission of the disease and 10-25 of patients suffering from depression are regarded as treatment-resistant In treatment resistant depression the use of a combination of antidepressive drugs is considered safe and effective However at present no data exist concerning the use of drug combination as primary therapeutic option The aim of the study is to examine the hypothesis that significantly more patients achieve full remission of depressive symptoms when treated with the combination of two antidepressants and as a secondary hypothesis that patients receiving a drug combination will achieve remission faster than patients treated with monotherapy To test these hypotheses a two group parallel design is used comparing the efficacy and safety of mirtazapine in combination with venlafaxine or placebo
Depressive disorder is one of the most common human diseases with a high burden for every patient herhis family health care system and society as a whole Actual treatment concepts of depressive disorders include pharmacologic biologic eg electroconvulsive therapy light therapy and psychologic therapy Even though effective therapeutic options are at hand therapy needs time It is often not possible to reach full remission of the disease and 10-25 of patients suffering from depression are regarded as treatment-resistant In treatment resistant depression the use of a combination of antidepressive drugs is considered safe and effective However at present no data exist concerning the use of drug combination as primary therapeutic option The aim of the study is to examine the hypothesis that significantly more patients achieve full remission of depressive symptoms when treated with the combination of two antidepressants and as a secondary hypothesis that patients receiving a drug combination will achieve remission faster than patients treated with monotherapy To test these hypotheses a two group parallel design is used comparing the efficacy and safety of mirtazapine in combination with venlafaxine or placebo
Detailed Description:
Background Information
Combining antidepressants is a well-established medical procedure for the treatment of therapy refractory depression that may also be applied successfully under non-refractory conditions The goal of the study is to test this hypothesis All participants are to be treated with Remergil Soltab a sedative antidepressant containing mirtazapine In a double-blind parallel-group design all participants are treated with either Trevilor retard an antidepressant of the selective-serotonin-norepinephrine-reuptake-inhibitor class containing venlafaxine or placebo
Especially in the treatment of therapy-resistant depression augmentation- and combination strategies are widely used Demling and Frieling 2004
Only limited data exist on the efficacy and safety of combination of antidepressants Carpenter et al have shown that adjunctive use of mirtazapine added to the prior used antidepressant mostly SSRIs was more effective than placebo Carpenter et al 2002 Devarajan and Dursun report a more effective antidepressive therapy with the combination of citalopram and reboxetine Devarajan and Dursun 2000 Rubio et al found the combination of reboxetine SSRI or venlafaxine and mirtazapine effective Rubio et al 2004 Smith et al report less side effects of venlafaxine use when combined with mirtazapine
All mentioned studies were conducted in treatment-resistant depression Only the study by Carpenter et al was done in a randomized controlled double-blind design No data exist on the efficacy and safety of combined antidepressant use as primary therapy of depression
Pallanti et al were able to show that combination of SSRI and mirtazapine leads to an earlier onset of therapeutic effects in OCD Pallanti et al 2004
There exists little evidence on the benefits of combined antidepressant use in depression However combination of antidepressants proved to be effective and safe in treatment-resistant depression All used antidepressants have side-effects see Fachinformation for further details Drug-drug interactions have not been described for the drugs used in the trial A risk-potentiation therefore seems unlikely
Route of administration
Venlafaxine and placebo are administered orally the usual mode of administration for antidepressive drugs Only Remergil Soltabis administered using an orodispersible tablet This way of administering mirtazapine has proven to be effective
Dosage
All participants are to be treated with Remergil Soltab 45mg the highest dosage of its license in Germany
Trevilor retard will be used 300mgd It is licensed for 375mgd but for practicability reasons especially blinding procedures the modestly lower dosage will be entertained
Dosage regimen
Remergil medication starts with 15mg for two days after randomization On day 3 and 4 30mg are used From day 5 on 45mg are used
In the Trevilor group treatment starts with 150mg for the first three days afterwards 300mg are used
Beginning with day 4 both groups are treated with two capsules of the blinded study medication
Treatment period
All patients are treated for 12 weeks in a double-blind fashion
The trial will be conducted in compliance with this protocol the guidelines for good clinical practice CPMPICH13595 and the applicable regulatory requirements namely the German law on drugs AMG
Participants
160 participants both female and male are to be recruited when admitted to the open wards of the Department of Psychiatry and Psychotherapy Universitätsklinikum Erlangen Participants have to suffer from depressive disorder and need to be 18-65 years old
Treatment of Subjects
After screening and inclusion into the trial all prior psychopharmacological medication is stopped and washed out How dose reduction and cessation is done will be decided individually The wash-out phase should not exceed 5-7 days The use of irreversible inhibitors of monoamine oxidase MAOI during 14 days prior to screening is an exclusion criterion as a wash-out period of 14 days is not suitable for the trial After the wash-out patients are randomized into two groups
1 VENLA - Participants receiving Trevilorretard 150mg in a blinded capsule For three days one capsule is administered afterwards two capsules are administered representing a dosage of 300mgd
2 CONT - Participants receiving placebo capsules For three days one capsule is administered afterwards two capsules are administered
All participants are receiving Remergil Soltab starting with 15mg for two days 30mg for days 3 and 4 and 45mg beginning with day 5
Medication permitted during the trial all non-psychiatric medication lorazepam and pipamperon
Medication not permitted Antidepressants other than the study medication neuroleptics other than pipamperon sedative other than lorazepam Medication with known interactions with the study medication according to the SPC
All medication is allowed before the wash-out period of the trial with the exception of irreversible MAO inhibitors MAOI
Medication permitted after the trial All medication is allowed after the trial The use of MAOI and other monoaminergic substances should not be started earlier than 14 days after the end of intake of study medication
Assessment of Efficacy
Efficacy is assessed using different psychometric scales either filled out by the participant or the investigator Scales to be used are BDI BAI BSI PSQuI as questionaires filled by the participant and CGI MADR-S HAM-D and HAM-A as rating scales filled out by the investigator During the first week and week 13 a cranial magnetic resonance image is obtained to assess morphologic changes of the brain
During the weekly visits BDI BAI CGI HAM-D HAM-A and MADR-S are entertained BSI and PSQuI are entertained at screening visit 4 visit 8 visit 12 and visit 13 please see also the attached flow chart and 16 Supplement A for further details
Combining antidepressants is a well-established medical procedure for the treatment of therapy refractory depression that may also be applied successfully under non-refractory conditions The goal of the study is to test this hypothesis All participants are to be treated with Remergil Soltab a sedative antidepressant containing mirtazapine In a double-blind parallel-group design all participants are treated with either Trevilor retard an antidepressant of the selective-serotonin-norepinephrine-reuptake-inhibitor class containing venlafaxine or placebo
Especially in the treatment of therapy-resistant depression augmentation- and combination strategies are widely used Demling and Frieling 2004
Only limited data exist on the efficacy and safety of combination of antidepressants Carpenter et al have shown that adjunctive use of mirtazapine added to the prior used antidepressant mostly SSRIs was more effective than placebo Carpenter et al 2002 Devarajan and Dursun report a more effective antidepressive therapy with the combination of citalopram and reboxetine Devarajan and Dursun 2000 Rubio et al found the combination of reboxetine SSRI or venlafaxine and mirtazapine effective Rubio et al 2004 Smith et al report less side effects of venlafaxine use when combined with mirtazapine
All mentioned studies were conducted in treatment-resistant depression Only the study by Carpenter et al was done in a randomized controlled double-blind design No data exist on the efficacy and safety of combined antidepressant use as primary therapy of depression
Pallanti et al were able to show that combination of SSRI and mirtazapine leads to an earlier onset of therapeutic effects in OCD Pallanti et al 2004
There exists little evidence on the benefits of combined antidepressant use in depression However combination of antidepressants proved to be effective and safe in treatment-resistant depression All used antidepressants have side-effects see Fachinformation for further details Drug-drug interactions have not been described for the drugs used in the trial A risk-potentiation therefore seems unlikely
Route of administration
Venlafaxine and placebo are administered orally the usual mode of administration for antidepressive drugs Only Remergil Soltabis administered using an orodispersible tablet This way of administering mirtazapine has proven to be effective
Dosage
All participants are to be treated with Remergil Soltab 45mg the highest dosage of its license in Germany
Trevilor retard will be used 300mgd It is licensed for 375mgd but for practicability reasons especially blinding procedures the modestly lower dosage will be entertained
Dosage regimen
Remergil medication starts with 15mg for two days after randomization On day 3 and 4 30mg are used From day 5 on 45mg are used
In the Trevilor group treatment starts with 150mg for the first three days afterwards 300mg are used
Beginning with day 4 both groups are treated with two capsules of the blinded study medication
Treatment period
All patients are treated for 12 weeks in a double-blind fashion
The trial will be conducted in compliance with this protocol the guidelines for good clinical practice CPMPICH13595 and the applicable regulatory requirements namely the German law on drugs AMG
Participants
160 participants both female and male are to be recruited when admitted to the open wards of the Department of Psychiatry and Psychotherapy Universitätsklinikum Erlangen Participants have to suffer from depressive disorder and need to be 18-65 years old
Treatment of Subjects
After screening and inclusion into the trial all prior psychopharmacological medication is stopped and washed out How dose reduction and cessation is done will be decided individually The wash-out phase should not exceed 5-7 days The use of irreversible inhibitors of monoamine oxidase MAOI during 14 days prior to screening is an exclusion criterion as a wash-out period of 14 days is not suitable for the trial After the wash-out patients are randomized into two groups
1 VENLA - Participants receiving Trevilorretard 150mg in a blinded capsule For three days one capsule is administered afterwards two capsules are administered representing a dosage of 300mgd
2 CONT - Participants receiving placebo capsules For three days one capsule is administered afterwards two capsules are administered
All participants are receiving Remergil Soltab starting with 15mg for two days 30mg for days 3 and 4 and 45mg beginning with day 5
Medication permitted during the trial all non-psychiatric medication lorazepam and pipamperon
Medication not permitted Antidepressants other than the study medication neuroleptics other than pipamperon sedative other than lorazepam Medication with known interactions with the study medication according to the SPC
All medication is allowed before the wash-out period of the trial with the exception of irreversible MAO inhibitors MAOI
Medication permitted after the trial All medication is allowed after the trial The use of MAOI and other monoaminergic substances should not be started earlier than 14 days after the end of intake of study medication
Assessment of Efficacy
Efficacy is assessed using different psychometric scales either filled out by the participant or the investigator Scales to be used are BDI BAI BSI PSQuI as questionaires filled by the participant and CGI MADR-S HAM-D and HAM-A as rating scales filled out by the investigator During the first week and week 13 a cranial magnetic resonance image is obtained to assess morphologic changes of the brain
During the weekly visits BDI BAI CGI HAM-D HAM-A and MADR-S are entertained BSI and PSQuI are entertained at screening visit 4 visit 8 visit 12 and visit 13 please see also the attached flow chart and 16 Supplement A for further details
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None