Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD

NCT01695291 | Completed Phase 2 Results DMC

• 2 other identifiers: 6574R34MH095502-03
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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 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.

Conditions

Obsessive Compulsive Disorder

Keywords

Obsessive compulsive disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).

  Change from Baseline at 12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.

Other: Placebo

Minocycline Augmentation

EXPERIMENTAL

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

Interventions

Minocycline DRUG

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.

Also known as: Minomycin, Minocin, Arestin, Aknemin, Solodyn and Dynacin

Minocycline Augmentation

Placebo OTHER

A placebo pill will be administered twice a day (BID) for 12 weeks.

Placebo

Eligibility Criteria

• Age: 8 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (2)

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Kelsey Hill, Research Coordinator
• Organization: New York State Psychiatric Institute

Kelsey.Hill@nyspi.columbia.edu

646-774-5793

Study Officials

• Moira A Rynn, M.D.

  Columbia University/NYSPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Chief

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: September 27, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2018
• Last Updated: November 13, 2019
• Results First Posted: March 13, 2019

Record last verified: 2019-10

Locations

US (2)