Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06537921
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-03-28
Brief Title:
Comorbid Obesity and Depression With an Anti-inflammatory Medication
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Feasibility Study in Comorbid Obesity and Treatment-Resistant Depression Using Minocycline as Adjunctive Treatment CODA
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CODA
Brief Summary:
Research suggests that only a subset of individuals with major depressive disorder MDD may benefit from anti-inflammatory treatments those who have C-reactive protein CRP 3 mgL a commonly used threshold for low-grade inflammation The emerging link between metabolic and immune abnormalities in MDD suggests that individuals with comorbid obesity and MDD are a subset of people who could particularly benefit from anti-inflammatory treatment The coexistence of obesity and MDD has been shown to amplify the risk of clinically elevated CRP levels 3mgL Therefore people with comorbid obesity MDD and CRP 3mgL could be an ideal target population in future randomised clinical trials RCTs However investigation into the feasibility and acceptability of inflammation-targeting treatment in this population is needed first
Meta-analyses identify minocycline a tetracycline antibiotic that can cross the blood-brain barrier as one of the most effective inflammation-targeting medications with antidepressant effects Minocycline can safely be used long-term at dosages of up to 200mg per day and has low tendency to lead to antibiotic resistance A pilot RCT of minocycline found a large effect size Cohens d098 p0001 for the reduction of MDD symptoms compared with placebo This effect size was even larger Cohens d15 p0005 in another RCT using minocycline when considering only participants with CRP 3mgL
One mechanism through which minocycline could ameliorate MDD symptoms appears to involve the activation of indoleamine 23-dioxygenase IDO which leads to an increase in the expression and function of the serotonin transporter Studies exploring this anti-inflammatory effect in MDD demonstrate that minocycline indeed can inhibit IDO
Another pathway through which minocycline could ameliorate MDD symptoms is through the reduction of inflammation at the central level Minocycline has been shown to reduce microglia activation in preclinical models Previous literature reports an impact of neuroinflammation on white matter microstructure and brain structure in patients with MDD and in individuals with obesity Minocyclines effect on white matter structure and myelination has not yet been investigated in humans in vivo Investigating whether neuroimaging biomarker candidates associated with neuroinflammation could be detected in this study design is needed
Meta-analyses identify minocycline a tetracycline antibiotic that can cross the blood-brain barrier as one of the most effective inflammation-targeting medications with antidepressant effects Minocycline can safely be used long-term at dosages of up to 200mg per day and has low tendency to lead to antibiotic resistance A pilot RCT of minocycline found a large effect size Cohens d098 p0001 for the reduction of MDD symptoms compared with placebo This effect size was even larger Cohens d15 p0005 in another RCT using minocycline when considering only participants with CRP 3mgL
One mechanism through which minocycline could ameliorate MDD symptoms appears to involve the activation of indoleamine 23-dioxygenase IDO which leads to an increase in the expression and function of the serotonin transporter Studies exploring this anti-inflammatory effect in MDD demonstrate that minocycline indeed can inhibit IDO
Another pathway through which minocycline could ameliorate MDD symptoms is through the reduction of inflammation at the central level Minocycline has been shown to reduce microglia activation in preclinical models Previous literature reports an impact of neuroinflammation on white matter microstructure and brain structure in patients with MDD and in individuals with obesity Minocyclines effect on white matter structure and myelination has not yet been investigated in humans in vivo Investigating whether neuroimaging biomarker candidates associated with neuroinflammation could be detected in this study design is needed
Detailed Description:
This is a single-centre feasibility using minocycline 200mgdaily in participants with comorbid obesity and major depressive disorder MDD The study aims to investigate the feasibility and acceptability of this proof-of-concept study in comorbid obesity and depression selected for elevated inflammation using adjunctive minocycline treatment
We will test in a 12-week feasibility proof-of-concept study whether individuals with comorbid obesity and treatment-resistant depression will complete an 8-week course of daily minocycline alongside their regular antidepressant treatment complete biomarker measurements eg blood saliva MRI and complete other outcome measurements eg questionnaires interviews Enrolment and retention rates will be monitored over the 12-week period The acceptability and suitability of all assessment measures will be examined Participant feedback of their activities will determine the acceptability of this study and assist refinement of the design in preparation for a future RCT The study will also aim to provide insight into the feasibility of using biomarkers of inflammation as well as pathways affected by minocycline towards the design of a future RCT in individuals with comorbid obesity and depression
Objective Determine the feasibility and acceptability of this protocol in comorbid obesity and depression using minocycline as adjunctive treatment
Minocycline dosing regimen After successful completion of the Screening Visit Visit 1 eligible subjects will be invited for the Baseline Visit 2 when they will be provided with the first bottle of minocycline oral capsules lasting 4 weeks At the 4-week mark subjects will return to the clinic to complete Visit 3 and associated visit procedures including returning the medication bottle and any remaining capsules Upon returning the bottle the pharmacy will dispense a second bottle for the subject once again containing minocycline for 4 weeks In total subjects will be taking minocycline for 8 weeks The dose of 200mg will be taken once daily
Study schedule
Following consent participants will be screened to ensure eligibility according to the inclusion and exclusion criteria as well as a small number of assessments including safety bloods to check liver and kidney functioning and questionnaires on mood medical and psychiatric history Furthermore we will ask each participants general practitioner GP for a summary of the participants medical records including current and past medications For females a pregnancy test will be done at all visits to ensure that they are not pregnant A small amount of blood no more than 10ml or about 2 teaspoons will be taken to check your levels of inflammation and some other tests to look at overall health and confirm CRP levels are suitably elevated at least 3mgL If following the screening participants are deemed eligible they will be invited for a baseline and then Week 4 Week 8 and Week 12 visits Simultaneously eligible participants will be sent a saliva sample collection kit in the post to complete at home and bring with them to their next visit In this kit will be 6 tubes saliva collection instructions and a diary to track your sample collections
At the Baseline visit 2 visit we will repeat some of the questionnaires from the previous visit along with some new questionnaires including some that ask about past stressful events how they have been feeling since the last visit and whether any medications have changed A sample of blood no more than 50ml or 3 tablespoons will be collected to check inflammation levels At this visit participants will also undergo their first brain MRI scan lasting approximately an hour During this visit participants will be given their first bottle of minocycline by a study doctor Participants will take 2 capsules each 100mg orally once a day in the mornings with breakfast for 28 consecutive days alongside their usual antidepressant A diary to track the use of minocycline any side effects or illness and any medications taken will be provided too as well as the 2nd saliva sample collection kit to be completed at home
At Week 4 visit 3 after 28 days 3 days of taking minocycline participants will return to the clinic for their next assessment The assessment and blood collection will be the same as those completed at Baseline No MRI will be conducted here Participants will also be given their 2nd bottle of minocycline dose the same as before to take for another 28 consecutive days As before participants should continue taking their antidepressant normally alongside this and continue completing their diary to track the use of minocycline any side effects and any other drugs taken With these a saliva sample collection kit will again be provided to complete at home
At Week 8 visit 4 after another 28 days 3 days of taking minocycline participants will return for their final in-person visit to the clinic All assessments including the MRI will be the same as those conducted at the Baseline visit The remaining minocycline will be returned to the research team and no new bottle will be dispensed - this is the end of the minocycline administration
Finally at Week 12 participants will be contacted by phone to complete the final set of questionnaires - the same set completed in person at the previous visits No blood or saliva samples will be collected at this time point
We will test in a 12-week feasibility proof-of-concept study whether individuals with comorbid obesity and treatment-resistant depression will complete an 8-week course of daily minocycline alongside their regular antidepressant treatment complete biomarker measurements eg blood saliva MRI and complete other outcome measurements eg questionnaires interviews Enrolment and retention rates will be monitored over the 12-week period The acceptability and suitability of all assessment measures will be examined Participant feedback of their activities will determine the acceptability of this study and assist refinement of the design in preparation for a future RCT The study will also aim to provide insight into the feasibility of using biomarkers of inflammation as well as pathways affected by minocycline towards the design of a future RCT in individuals with comorbid obesity and depression
Objective Determine the feasibility and acceptability of this protocol in comorbid obesity and depression using minocycline as adjunctive treatment
Minocycline dosing regimen After successful completion of the Screening Visit Visit 1 eligible subjects will be invited for the Baseline Visit 2 when they will be provided with the first bottle of minocycline oral capsules lasting 4 weeks At the 4-week mark subjects will return to the clinic to complete Visit 3 and associated visit procedures including returning the medication bottle and any remaining capsules Upon returning the bottle the pharmacy will dispense a second bottle for the subject once again containing minocycline for 4 weeks In total subjects will be taking minocycline for 8 weeks The dose of 200mg will be taken once daily
Study schedule
Following consent participants will be screened to ensure eligibility according to the inclusion and exclusion criteria as well as a small number of assessments including safety bloods to check liver and kidney functioning and questionnaires on mood medical and psychiatric history Furthermore we will ask each participants general practitioner GP for a summary of the participants medical records including current and past medications For females a pregnancy test will be done at all visits to ensure that they are not pregnant A small amount of blood no more than 10ml or about 2 teaspoons will be taken to check your levels of inflammation and some other tests to look at overall health and confirm CRP levels are suitably elevated at least 3mgL If following the screening participants are deemed eligible they will be invited for a baseline and then Week 4 Week 8 and Week 12 visits Simultaneously eligible participants will be sent a saliva sample collection kit in the post to complete at home and bring with them to their next visit In this kit will be 6 tubes saliva collection instructions and a diary to track your sample collections
At the Baseline visit 2 visit we will repeat some of the questionnaires from the previous visit along with some new questionnaires including some that ask about past stressful events how they have been feeling since the last visit and whether any medications have changed A sample of blood no more than 50ml or 3 tablespoons will be collected to check inflammation levels At this visit participants will also undergo their first brain MRI scan lasting approximately an hour During this visit participants will be given their first bottle of minocycline by a study doctor Participants will take 2 capsules each 100mg orally once a day in the mornings with breakfast for 28 consecutive days alongside their usual antidepressant A diary to track the use of minocycline any side effects or illness and any medications taken will be provided too as well as the 2nd saliva sample collection kit to be completed at home
At Week 4 visit 3 after 28 days 3 days of taking minocycline participants will return to the clinic for their next assessment The assessment and blood collection will be the same as those completed at Baseline No MRI will be conducted here Participants will also be given their 2nd bottle of minocycline dose the same as before to take for another 28 consecutive days As before participants should continue taking their antidepressant normally alongside this and continue completing their diary to track the use of minocycline any side effects and any other drugs taken With these a saliva sample collection kit will again be provided to complete at home
At Week 8 visit 4 after another 28 days 3 days of taking minocycline participants will return for their final in-person visit to the clinic All assessments including the MRI will be the same as those conducted at the Baseline visit The remaining minocycline will be returned to the research team and no new bottle will be dispensed - this is the end of the minocycline administration
Finally at Week 12 participants will be contacted by phone to complete the final set of questionnaires - the same set completed in person at the previous visits No blood or saliva samples will be collected at this time point
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