Major Depressive DisorderPhase 1/2NCT04088448
The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients
A Phase 1/2 study testing Metformin in people with Major Depressive Disorder, run by Sadat City University at 1 site in Egypt.
Trial summary
The aim of our study was to test whether the combined administration of the SSRI fluoxetine and metformin, a drug improving metabolic profile and therefore potentially able to mimic the influence of supportive living conditions on treatment outcome, results in an improved antidepressant efficacy compared with… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2017to 1 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without psychotic features and a total 17 item HAM-D score of at least 18 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).
- Patients were requested to be free of all the psychotropic and anti-inflammatory medications for at least 4 weeks before participating in the study.
Who cannot join
- Patients with bipolar I or bipolar II disorder
- Patients with personality disorders
- Patients with eating disorders
- Patients with substance dependence or abuse
- Patients with concurrent active medical condition
- Patients with history of seizures
Show all 10Show fewer
- Patients with history of receiving Electroconvulsive therapy (ECT)
- Patients with diabetes and other inflammatory disorders
- Patients with allergy or contraindications to the used medications
- Patients with finally pregnant or lactating females
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial
The aim of our study was to test whether the combined administration of the SSRI fluoxetine and metformin, a drug improving metabolic profile and therefore potentially able to mimic the influence of supportive living conditions on treatment outcome, results in an improved antidepressant efficacy compared with fluoxetine alone.
Read the detailed description
Selective Serotonin Reuptake Inhibitors (SSRIs) represent the standard treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete. In order to explain, at least in part, such variable efficacy, we have shown that SSRI administration does not affect mood per se but, by enhancing neural plasticity, amplifies the influence of the living conditions on mood. Consequently, in a favorable environment, SSRI treatment leads to a reduction of symptoms while, in stressful conditions, it could lead to a worse prognosis. Here, we test the hypothesis that, given the clear association between living conditions and metabolic profile, the modulation of the latter may mimic the effect of the environment on SSRI outcome, determining treatment efficacy.
Metformin is widely used as a first line treatment for patients with type 2 diabetes mellitus for more than 60 years for the reduction of hepatic glucose output and increase of the insulin mediated utilization of glucose. Previous studies demonstrated that metformin can rapidly cross the blood brain barrier and has several beneficial effects in the brain such as anti-inflammatory and neuroprotective effects. Furthermore, metformin, along with its anti-glycemic effects, has been documented to possess anti-depression effects in patients with type 2 diabetes. In Guo's study, 58 participants diagnosed with depression and type 2 diabetes were divided into two groups: one treated with metformin and the other with a placebo for 24 weeks. Analysis of MADRS and HRSD-17 scores showed that metformin significantly reduced MADRS scores and HRSD-17 scores. Metformin administration improves depressive symptoms in type 2 diabetes mellitus.
- Conditions
- Major Depressive Disorder
- Being tested
- Placebo oral tablet, Metformin
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo oral tabletDrug
Fluoxetine 20 mg capsule plus Placebo tablet administered once daily after food
MetforminDrug
Fluoxetine 20 mg capsule plus Metformin 1000 mg extended release tablet administered once daily after food
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Fluoxetine 20 mg capsule once daily for 12 week plus placebo tablet once daily for 12 weeks Receives: Drug: Placebo oral tablet |
| Metformin group | Experimental | Fluoxetine 20 mg capsule once daily for 12 week plus Metformin 1000 mg XR tablet once daily for 12 weeks Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect on Hamilton Depression rating scale score (HAM-D score)
The principal measure of the outcome was the 17-items HAM-D. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-13 suggest mild depression, 14-17 moderate depression and scores over 17 are indicative of severe depression. Remission is defined as HAM-D total score ≤ 7 (primary outcome). Treatment response is defined as ≥ 50% drop in the HAM-D total score.
Measured: Baseline to week 12
Secondary outcomes (4)
TNF-α
Serum level of tumor necrosis factor alpha (TNF-α)
Measured: Baseline to week 12
BDNF
Serum level of brain derived neurotrophic factor (BDNF),
Measured: Baseline to week 12
CRP
Serum level of C-Reactive Protein
Measured: Baseline to week 12
IGF-1
Serum level of Insulin-Like Growth Factor
Measured: Baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2019
- Study start1 Jan 2017
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sadat City University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahmoud Samy Abdallah, Sadat City University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088448
- Sponsor's protocol ID
- 0056/2018
- Status last verified
- Jun 2020
- First submitted
- 11 Sep 2019
- Last updated
- 16 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Abdallah MS, Mosalam EM, Zidan AA, Elattar KS, Zaki SA, Ramadan AN, Ebeid AM. The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. Neurotherapeutics. 2020 Oct;17(4):1897-1906. doi: 10.1007/s13311-020-00878-7.
PubMed 32500486
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT04088448
- Acronym / sponsor ID
- 0056/2018
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Sadat City UniversityUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 12 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of our study was to test whether the combined administration of the SSRI fluoxetine and metformin, a drug improving metabolic profile and therefore potentially able to mimic the influence of supportive living conditions on treatment outcome, results in an improved antidepressant efficacy compared with fluoxetine alone.
Detailed description
Selective Serotonin Reuptake Inhibitors (SSRIs) represent the standard treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete. In order to explain, at least in part, such variable efficacy, we have shown that SSRI administration does not affect mood per se but, by enhancing neural plasticity, amplifies the influence of the living conditions on mood. Consequently, in a favorable environment, SSRI treatment leads to a reduction of symptoms while, in stressful conditions, it could lead to a worse prognosis. Here, we test the hypothesis that, given the clear association between living conditions and metabolic profile, the modulation of the latter may mimic the effect of the environment on SSRI outcome, determining treatment efficacy.
Metformin is widely used as a first line treatment for patients with type 2 diabetes mellitus for more than 60 years for the reduction of hepatic glucose output and increase of the insulin mediated utilization of glucose. Previous studies demonstrated that metformin can rapidly cross the blood brain barrier and has several beneficial effects in the brain such as anti-inflammatory and neuroprotective effects. Furthermore, metformin, along with its anti-glycemic effects, has been documented to possess anti-depression effects in patients with type 2 diabetes. In Guo's study, 58 participants diagnosed with depression and type 2 diabetes were divided into two groups: one treated with metformin and the other with a placebo for 24 weeks. Analysis of MADRS and HRSD-17 scores showed that metformin significantly reduced MADRS scores and HRSD-17 scores. Metformin administration improves depressive symptoms in type 2 diabetes mellitus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: Placebo oral tabletFluoxetine 20 mg capsule once daily for 12 week plus placebo tablet once daily for 12 weeks |
| Metformin group | Experimental | Drug: MetforminFluoxetine 20 mg capsule once daily for 12 week plus Metformin 1000 mg XR tablet once daily for 12 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without psychotic features and a total 17 item HAM-D score of at least 18 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).
- Patients were requested to be free of all the psychotropic and anti-inflammatory medications for at least 4 weeks before participating in the study.
Key exclusion criteria (10 listed)
- Patients with bipolar I or bipolar II disorder
- Patients with personality disorders
- Patients with eating disorders
- Patients with substance dependence or abuse
- Patients with concurrent active medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo oral tabletFluoxetine 20 mg capsule plus Placebo tablet administered once daily after food | Drug | Control group |
| MetforminFluoxetine 20 mg capsule plus Metformin 1000 mg extended release tablet administered once daily after food | Drug | Metformin group |
Primary outcome
Effect on Hamilton Depression rating scale score (HAM-D score)
Time frame: Baseline to week 12
The principal measure of the outcome was the 17-items HAM-D. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-13 suggest mild depression, 14-17 moderate depression and scores over 17 are indicative of severe depression. Remission is defined as HAM-D total score ≤ 7 (primary outcome). Treatment response is defined as ≥ 50% drop in the HAM-D total score.
4 secondary outcomes
TNF-α
Time frame: Baseline to week 12
BDNF
Time frame: Baseline to week 12
CRP
Time frame: Baseline to week 12
IGF-1
Time frame: Baseline to week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Derived from this study: PubMed 32500486Abdallah MS, Mosalam EM, Zidan AA, Elattar KS, Zaki SA, Ramadan AN, Ebeid AM. The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial. Neurotherapeutics. 2020 Oct;17(4):1897-1906. doi: 10.1007/s13311-020-00878-7.
- The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled TrialLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Metformin in people with Major Depressive Disorder, run by Sadat City University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect on Hamilton Depression rating scale score (HAM-D score) (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04088448, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.