Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD

A Randomized, Placebo-controlled Trial of Minocycline Added to Serotonin Reuptake Inhibitors in Pediatric OCD: Examining the Effects on Clinical Symptoms and on Brain Glutamate Levels Using MRS Imaging

This study will examine the feasibility and potential efficacy of augmenting SRIs with minocycline. The study will assess whether the addition of minocycline leads to measurable changes in striatal glutamate (Glu) levels. This study will recruit up to 45 youth ages 8-20 diagnosed with clinically significant OCD who have demonstrated no more than minimal response to SRI treatment and are currently on a stable dose of SRI medication for at least 12 weeks. Participants will be randomized to receive either 12 weeks of minocycline treatment or pill placebo. Randomization will be 2:1 so that 2 of 3 participants receive minocycline. Screening for eligibility will take place for 1-4 weeks. Participants will undergo magnetic resonance spectroscopy (MRS) scans to measure striatal Glu levels prior to randomization, and again immediately following the treatment period. During the treatment period, participants will meet initially weekly and then every other week with the study psychiatrist. All participants will be offered three months of open medication treatment following participation. The clinical trial will only be conducted at the New York State Psychiatric Institute (NYSPI) and the MRS scans may be conducted at Weill Cornell Medical Center or NYSPI.

Study Overview

• Status: Completed
• Conditions: Obsessive Compulsive Disorder
• Intervention / Treatment: Other: Placebo; Drug: Minocycline

Detailed Description

Please see the brief summary for study description.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must be ages of 8-20 at the time of consent
• Participants must weigh at least 25kg
• Participants and a parent/guardian must be able to read and understand English
• Participants must meet diagnostic criteria for obsessive-compulsive disorder with score ≥ 16 on the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS)
• Participants must be on stable dose of serotonin reuptake inhibitor (SRI) medication, and must have had a minimal adequate trial of SRI medication
• Report of at least minimal, but not full, response to current SRI medication to warrant ongoing SRI treatment
• For participants younger than 18, written informed assent by the participant and consent by the parent. For participants 18 and older, written consent by the participant and permission for legal guardian/parent to provide information

Exclusion Criteria:

• Lifetime diagnosis of: psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, mental retardation, or substance/alcohol dependence
• Current diagnosis of major depressive disorder, Tourette's/Tic Disorder, or substance/alcohol abuse
• Positive urine screen for illicit drugs
• Medical or psychiatric conditions that would make participation in the study unsafe
• Active suicidal ideation
• Females who are using hormonal birth control
• Presence of metallic device or dental braces incompatible with MRS
• Intelligence quotient (IQ) <80
• OCD patients with primary symptoms of hoarding (determined by CYBOCS checklist)
• Current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
• Individuals who are currently receiving Exposure and Response Prevention therapy and are in the acute phase of treatment.
• Documented history of hypersensitivity or intolerance to tetracycline antibiotics
• Use of medications that are contra-indicated with minocycline (e.g., concomitant use of antacids, iron, calcium, magnesium, aluminum, zinc salts as they impair minocycline absorption; of anti-coagulant drugs as minocycline has been shown to depress plasma prothrombin activity; of other antibiotics or Accutane due to the rare side effect of pseudotumor cerebri)
• Inability of participant or parent/guardian to read or understand English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.	Other: Placebo; A placebo pill will be administered twice a day (BID) for 12 weeks.
Experimental: Minocycline Augmentation; Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.	Drug: Minocycline; Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.; Other Names: Minomycin, Minocin, Arestin, Aknemin, Solodyn and Dynacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)	The Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) is a semi-structured measure of Obsessive-Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the adult YBOCS only in its use of simpler language. The total CYBOCS score ranges from 0 to 40, with higher scores indicating more severe symptomatology.	Change from Baseline at 4, 8, and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).	The change in striatal glutamate level will be assessed.	Change from Baseline at 12 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH); Weill Medical College of Cornell University
• Investigators: Principal Investigator: Moira A Rynn, M.D., Columbia University/NYSPI

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 27, 2012

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Obsessive compulsive disorder
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: 6574; R34MH095502-03 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No