Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01695291
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Weill Medical College of Cornell University (Other)
• Enrollment: 31
• Locations: 2
• Arms: 2
• Actual Duration (Months): 72
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

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

• Study Type: Interventional
• Actual Enrollment: 31 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
• Actual Study Start Date: May 1, 2012
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) [Change from Baseline at 4, 8, and 12 weeks]

   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.

Secondary Outcome Measures

1. Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS). [Change from Baseline at 12 weeks]

   The change in striatal glutamate level will be assessed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical Center	New York	New York	United States	10021
2	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

Study Documents (Full-Text)

• Study Protocol - Mar 23, 2018
• Statistical Analysis Plan - Jan 7, 2019

More Information

Publications

None provided.

• Responsible Party: Helen Blair Simpson, Research Chief, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01695291
• Other Study ID Numbers: 6574; R34MH095502-03
• First Posted: Sep 27, 2012
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Helen Blair Simpson, Research Chief, New York State Psychiatric Institute: Obsessive compulsive disorder
• Additional relevant MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Minocycline

Study Results

Participant Flow

Arm/Group Title	Placebo	Minocycline Augmentation
Arm/Group Description	Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication. Placebo: A placebo pill will be administered twice a day (BID) for 12 weeks.	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. 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.
Period Title: Overall Study
STARTED	10	21
COMPLETED	8	14
NOT COMPLETED	2	7

Baseline Characteristics

Arm/Group Title	Placebo	Minocycline Augmentation	Total
Arm/Group Description	Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication. Placebo: A placebo pill will be administered BID for 12 weeks.	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. 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.	Total of all reporting groups
Overall Participants	10	21	31
Age (Count of Participants)
<=18 years	8 80%	16 76.2%	24 77.4%
Between 18 and 65 years	2 20%	5 23.8%	7 22.6%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 50%	11 52.4%	16 51.6%
Male	5 50%	10 47.6%	15 48.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	1 4.8%	2 6.5%
Not Hispanic or Latino	8 80%	20 95.2%	28 90.3%
Unknown or Not Reported	1 10%	0 0%	1 3.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 10%	0 0%	1 3.2%
Asian	2 20%	1 4.8%	3 9.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 4.8%	1 3.2%
White	5 50%	19 90.5%	24 77.4%
More than one race	2 20%	0 0%	2 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	21 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)
Description	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.
Time Frame	Change from Baseline at 4, 8, and 12 weeks

Outcome Measure Data

Analysis Population Description

Due to the early-termination of some participants, not all completed the CYBOCS at Week 12

Arm/Group Title	Placebo	Minocycline Augmentation
Arm/Group Description	Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication. Placebo: A placebo pill will be administered BID for 12 weeks.	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. 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.
Measure Participants	10	21
Baseline	28.20 (3.79)	29.0 (3.49)
Week 4	26.67 (4.69)	27.11 (5.61)
Week 8	25.33 (5.22)	25.47 (5.77)
Week 12	26.44 (5.10)	25.59 (6.39)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Due to the early-termination of some participants, not all completed MRS at Week 12

Arm/Group Title	Placebo	Minocycline Augmentation
Arm/Group Description	Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication. Placebo: A placebo pill will be administered BID for 12 weeks.	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. 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.
Measure Participants	9	17
Baseline	44.49 (6.76)	43.96 (9.18)
Week 12	42.97 (8.25)	39.35 (6.47)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Placebo		Minocycline Augmentation
Arm/Group Description	Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication. Placebo: A placebo pill will be administered BID for 12 weeks.		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. 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.
All Cause Mortality
	Placebo		Minocycline Augmentation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/21 (0%)
Serious Adverse Events
	Placebo		Minocycline Augmentation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		5/21 (23.8%)
Psychiatric disorders
Hospitalization	0/10 (0%)		2/21 (9.5%)
Worsening of OCD symptoms and an interrupted suicide attempt	0/10 (0%)		1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Significant esophagitis	0/10 (0%)		1/21 (4.8%)
Skin and subcutaneous tissue disorders
Drug Rash	0/10 (0%)		1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Placebo		Minocycline Augmentation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		21/21 (100%)
Cardiac disorders
Heart racing or skipping beats	0/10 (0%)		3/21 (14.3%)
Gastrointestinal disorders
Stomach ache or cramps	1/10 (10%)		1/21 (4.8%)
Diarrhea	1/10 (10%)		1/21 (4.8%)
General disorders
Dry mouth	1/10 (10%)		1/21 (4.8%)
More thirsty	1/10 (10%)		2/21 (9.5%)
Headache	1/10 (10%)		4/21 (19%)
Dizzy or light-headed	0/10 (0%)		2/21 (9.5%)
Metabolism and nutrition disorders
Lost weight	1/10 (10%)		1/21 (4.8%)
Feeling hungry	1/10 (10%)		2/21 (9.5%)
Gained weight	1/10 (10%)		0/21 (0%)
Less hungry	0/10 (0%)		2/21 (9.5%)
Musculoskeletal and connective tissue disorders
Muscles weak	1/10 (10%)		2/21 (9.5%)
Psychiatric disorders
Irritable or bad mood	2/10 (20%)		5/21 (23.8%)
Angry or hostile	1/10 (10%)		6/21 (28.6%)
Sad or low mood	4/10 (40%)		7/21 (33.3%)
Lack of interest	4/10 (40%)		6/21 (28.6%)
Feeling shutdown	4/10 (40%)		3/21 (14.3%)
Mood swings	3/10 (30%)		5/21 (23.8%)
Anxious, tense, uptight	2/10 (20%)		6/21 (28.6%)
Lack of self-control/impulsive	4/10 (40%)		1/21 (4.8%)
Trouble paying attention	3/10 (30%)		3/21 (14.3%)
Racing thoughts	4/10 (40%)		3/21 (14.3%)
Can't sit or stand still	4/10 (40%)		7/21 (33.3%)
Tired/fatigued	5/10 (50%)		5/21 (23.8%)
Sleep too much	2/10 (20%)		8/21 (38.1%)
Trouble falling or staying asleep	3/10 (30%)		4/21 (19%)
Skin and subcutaneous tissue disorders
Pimples or acne	1/10 (10%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.