Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD

Study Description

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Brief Summary:

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 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 NYSPI and the MRS scans may be conducted at Weill Cornell Medical Center or NYSPI.

Condition or disease	Intervention/treatment	Phase
Obsessive Compulsive Disorder	Drug: Minocycline; Other: Placebo	Phase 2

Detailed Description:

Please see the brief summary for study description.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	33 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	May 2012
Actual Primary Completion Date :	February 2017
Estimated Study Completion Date :	March 2018

Arms and Interventions

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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 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 Name: Minomycin, Minocin, Arestin, Aknemin, Solodyn and Dynacin

Outcome Measures

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Primary Outcome Measures :

1. Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS) [ Time Frame: Change from Baseline at 4, 8, and 12 weeks ]
   The CYBOCS is a semi-structured measure of 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.

Secondary Outcome Measures :

1. Striatal glutamate level measured by MRS. [ Time Frame: Change from Baseline at 12 weeks ]
   The change in striatal glutamate level will be assessed.

Eligibility Criteria

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Ages Eligible for Study:	8 Years to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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
• 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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

New York State Psychiatric Institute

National Institute of Mental Health (NIMH)

Weill Medical College of Cornell University

Investigators

Principal Investigator:	Moira A Rynn, M.D.	Columbia University/NYSPI

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT01695291 History of Changes
Other Study ID Numbers:	6574; R34MH095502-03 ( U.S. NIH Grant/Contract )
First Posted:	September 27, 2012
Last Update Posted:	March 30, 2017
Last Verified:	March 2017

Keywords provided by New York State Psychiatric Institute:

Obsessive compulsive disorder

Additional relevant MeSH terms:

Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Personality Disorders; Mental Disorders; Anxiety Disorders; Minocycline; Serotonin Uptake Inhibitors; Anti-Bacterial Agents	Anti-Infective Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs