Clinical trial NCT03580967: Vortioxetine Monotherapy for Major Depressive Disorder in Type 2 Diabetes
Official title: Vortioxetine Monotherapy for Major Depressive Disorder in Type 2 Diabetes: Role of Inflammation, Kynurenine Pathway, and Structural and Functional Brain Connectivity as Biomarkers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Type2 Diabetes
Major Depressive Disorder
Keywords: Type 2 Diabetes
Major Depressive Disorder
Vortioxetine
Lead sponsor: Loyola University
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2018-07-10
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will receive a 10 or 20 mg dose of vortioxetine to take daily for 8 weeks. Study PI and sub-investigator (psychiatrist Murali Rao, MD) will determine appropriate dose.
Primary purpose: TREATMENT

Brief summary: This study will enroll participants who have been diagnosed with type 2 diabetes and are experiencing symptoms of depression. This study will look at an anti-depressant medication called vortioxetine (Trintellix). Vortioxetine is an oral medication (pill) that has been approved by the US Food and Drug Administration (FDA) to treat depression in adults.

The purpose of this study is to look at what effects (if any) vortioxetine may have on symptoms of depression in patients with type 2 diabetes. This study will also look at what effects (if any) vortioxetine has on blood sugar, and how vortioxetine may improve the way our brains are able to adapt and respond to stress.

Detailed description: This will be a 9-week, open-label, single-arm, pilot investigation for Type 2 Diabetes (T2D) patients with Major Depressive Disorder (MDD). The study includes a screening visit, a 1-week washout phase (or 30-day washout phase for serotonergic agents), and an 8-week flexible dose phase that includes the baseline and post-treatment follow-up visits. A minimum of N=70 participants will be enrolled in the treatment.

At the screening visit, the study will be explained and the informed consent process will take place. Patients who sign the IRB-approved consent form will undergo a psychiatric interview. The diagnosis of MDD will be established in this examination using the psychiatric interview and Hamilton Depression Rating Scale (HAM-D) by the study PI.

Eligible participants will be instructed how to taper the antidepressant they have been taking (if relevant) over the course of the one-week (or 30-days for serotonergic agents).

After these tapers, all participants will return for a baseline visit where they will be re-assessed to ensure persistent depressive symptoms. If patients continue to score ≥18 on the HAM-D, they will complete the psychosocial questionnaires; patients scoring below \<18 on the HAM-D at this visit will be terminated from the study and offered conventional, standard of care treatment within LUMC Department of Psychiatry. Once participants are given the psychosocial questionnaires as part of the baseline visit, a blood draw will be conducted by the Study Nurse/Coordinator, and MRI scans will be completed.

At the end of the baseline session, participants will receive Vortioxetine for the remaining 8-week flexible dosing period (i.e., 10 mg to 20 mg dosing). In the instance a patient is unable to tolerate either 10 mg to 20 mg of Vortioextine (as reported in the medication packet insert), the patient will be allowed to reduce their dosage to 5 mg, which will be done in consultation with the PI and sub-investigator.

Following the 8-week intervention, participants will be scheduled for the post visit, which will include the following: another clinical interview and HAM-D conducted by the PI, completion of post visit-related psychosocial questionnaires, a second blood draw conducted by the Study Nurse/Coordinator, and then post visit-MRI scans will be completed. Should any patients continue to score \>18 on the HAM-D at study conclusion, resources and referrals will be provided for further psychological/psychiatric interventions, as needed.

Eligibility criteria: Inclusion Criteria:

* Adults 40 to 65 years of age at time of screening visit.
* Women only: Must be post-menopausal at time of screening visit (i.e., defined by NO menstruation for at least the past 12-months).
* Diagnosis of T2D, as defined by a diagnosis of T2D (for at least 12 months) in the medical record made by a physician (i.e., denoted as 250.XX according to ICD-9/ICD-10 billing codes) OR
* current use of oral hypoglycemic medications or insulin OR
* having a fasting plasma glucose ≥126 mg/dL in the medical record OR
* having a 2-hour oral glucose tolerance test ≥200 mg/dL in the medical record
* Patients who meet criteria for current MDD without significant co-morbid psychiatric diagnoses, as determined by study PI from screening visit:
* Clinical Psychiatric Interview to determine DSM-V criteria for current MDD AND
* A minimum score of 18 on the Hamilton Depression Scale (HAM-D)
* Patients with T2D and current MDD that would benefit from antidepressant therapy, which may include:
* Patients with current MDD who were NOT prescribed an antidepressant medication in the past;
* Patients with current MDD who are NOT responding to their current prescribed antidepressant;
* Patients with current MDD who are experiencing breakthrough depressive symptoms despite being maintained on another antidepressant.
* Must have the ability to provide informed consent to participate in the study.

Exclusion Criteria:

* Patients with any form of contraindication to Vortioxetine treatment, as outlined in the medication packet insert, (e.g., presence of a known hypersensitivity to the study drug or hypersensitivity to MAO-I use, etc.).

MRI-Related Exclusion Criteria

* Participants weighing \>550 lbs (per MRI weight restrictions set by Loyola University Medical Center);
* Patients with a pacemaker, AICD, ossicular prosthesis, nerve stimulator, or another contraindication to MRI;
* Pregnant patients;
* Patients with an inability to tolerate being in enclosed places/spaces such as MRI;
* Patients with a history of neurosurgery, brain irradiation, or cerebral endovascular treatment.;
* Patients with history of epilepsy, stroke, neurodegenerative disorder, severe traumatic brain injury, hydrocephalus or demyelinating disorder;
* Patients with a history of malignant neoplasm

Exclusion Criteria to Reduce False Positive Rates of Inflammation

* Specific pre-existing chronic pain conditions such as rheumatoid arthritis or fibromyalgia. However, this will NOT include more localized pain-related conditions such as low-back pain or complications associated with T2D (e.g., diabetic neuropathy).
* History of peptic ulcer complicated by perforation, hemorrhage, or obstruction; symptoms of peptic ulcer within 4 weeks of enrollment date that has not been treated.
* Current diagnosis of substance abuse/dependence during the 6 months prior to study enrollment.
* Current diagnosis of uncontrolled hypertension, anemia, liver disease, kidney disease, stroke, and autoimmune disease. Based on the clinical judgment of the study PI, a risk assessment will be conducted if a participant endorses any of these diagnoses but would be otherwise a suitable participant to enroll in the study.
* Current acute infection/infectious disease (i.e., a cold or the flu). Based on the clinical judgement of the study PI, a risk assessment will be conducted if a participant endorses some acute infection/infectious disease, but would be otherwise suitable to enroll in the study following a brief wait period for full symptom remission.
* Pre- and peri-menopausal women (i.e., defined as the presence of ANY menstruation within the past 12 months).
* Certain steroids (e.g., use of hormonal birth control) and any systemic corticosteroids. Please note that hormone replacement therapy will be allowed along with any topical corticosteroid creams.
* Patients currently enrolled in any other clinical trial for treatment of MDD (e.g., patients receiving experimental vitamin D supplementation).

Primary outcomes:
measure: Change in depressive symptoms measured by Hamilton Depression Rating Scale (HAM-D)
timeFrame: Baseline and End of Treatment visit (Week 8)
Secondary outcomes:
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: Loyola University Chicago
name: Todd Doyle, PhD
role: PRINCIPAL_INVESTIGATOR
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