NCT00271219

Brief Summary

Children born to women who abuse drugs have a high risk of being born with birth defects and developmental problems. Methadone is a drug that is commonly used for treating opioid dependence. However, its use by a pregnant woman can cause severe withdrawal symptoms in a newborn because of the prenatal exposure. The purpose of this study is to evaluate the effectiveness of buprenorphine, another drug, versus methadone in reducing withdrawal symptoms in children born to opioid-dependent women.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
175

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jul 2005

Longer than P75 for phase_3

Geographic Reach
3 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2005

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

December 28, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 30, 2005

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2009

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2010

Completed
5.2 years until next milestone

Results Posted

Study results publicly available

August 5, 2015

Completed
Last Updated

August 5, 2015

Status Verified

July 1, 2015

Enrollment Period

4.1 years

First QC Date

December 28, 2005

Results QC Date

March 11, 2013

Last Update Submit

July 30, 2015

Conditions

Opioid Related DisordersPregnancyOpioid Dependence

Keywords

opiate addictionopiate dependencesubstance abuseaddictionsubstance addictionpregnancybuprenorphinemethadonefetalneonatalpost-partum

Outcome Measures

Primary Outcomes (5)

  • Child's Head Circumference Measurement (Measured at Birth)

    birth

  • Child's Length of Hospital Stay

    delivery until hospital discharge (min=2 days, max=79 days)

  • Number of Children Requiring Treatment for Neonatal Abstinence Signs (NAS)

    Neonatal abstinence syndrome (NAS) characterized by hyperirritability of the central nervous system and dysfunction in the autonomic nervous system, gastrointestinal tract, and respiratory system.11 When left untreated, NAS can result in serious illness (e.g., diarrhea, feeding difficulties, weight loss, and seizures) and death.

    From birth until hospital discharge (min=4 days, max=10, depending on site)

  • Child's Peak Daily Total NAS Score

    NAS was measured with the MOTHER NAS scale, which includes 28 items, 19 of which are used for scoring and medication decisions. Scores can range from 0 to 42, with higher scores indicating more severe withdrawal.

    minimum twice daily from birth until NAS no longer measured (min=10 days)

  • Total Amount of Morphine Sulfate That a Neonate Receives to Treat NAS

    Total amount in mg

    Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days)

Secondary Outcomes (4)

  • Mother's Self-report of Drug Use (Measured Monthly by Time Line Follow Back)

    monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)

  • Mother's HIV Risk Behaviors (Measured Monthly by Risk Behavior Assessment)

    monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)

  • Mother's Measures of Dose Adequacy and Acceptance Over Time (Measured Weekly by Dose Adequacy Measure)

    from study entry until discontinuation or delivery (min=29 days, max=239 days)

  • Mother's Psychosocial Functioning at Delivery as Measured by the Addiction Severity Index Psychosocial Index Score

    at delivery

Study Arms (2)

Buprenorphine

EXPERIMENTAL

Buprenorphine

Drug: Buprenorphine

Methadone

ACTIVE COMPARATOR

Methadone

Drug: Methadone

Interventions

MethadoneDRUG

daily oral dosing 20-140 mg

Methadone
BuprenorphineDRUG

sl daily 2-32 mg

Buprenorphine

Eligibility Criteria

Age18 Years - 41 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Current opioid dependence
  • Current opioid use, as determined by a urine drug test
  • Pregnant with a single child with a gestational age of 6 to 30 weeks, as determined by a sonogram

You may not qualify if:

  • Current medical condition that would make study participation dangerous, as determined by study physician
  • Diagnosed with an acute, severe psychiatric illness
  • Current SCID I-E module diagnosis of benzodiazepine or alcohol abuse
  • Use of alcohol or benzodiazepines in the 30 days prior to study entry, as determined by the Addiction Severity Index
  • Pending legal action that may prohibit or interfere with study participation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Wayne State University

Detroit, Michigan, 48207, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Brown University

Providence, Rhode Island, 02912, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Medical University of Vienna

Vienna, A1090, Austria

Location

St. Joseph's Health Centre

Toronto, Ontario, M6R 1B5, Canada

Location

Related Publications (14)

  • Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR. Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Am J Addict. 2012 Nov;21 Suppl 1:S1-4. doi: 10.1111/j.1521-0391.2012.00289.x.

    PMID: 23786504DERIVED

  • Holbrook AM, Jones HE, Heil SH, Martin PR, Stine SM, Fischer G, Coyle MG, Kaltenbach K. Induction of pregnant women onto opioid-agonist maintenance medication: an analysis of withdrawal symptoms and study retention. Drug Alcohol Depend. 2013 Sep 1;132(1-2):329-34. doi: 10.1016/j.drugalcdep.2013.02.031. Epub 2013 Mar 21.

    PMID: 23523131DERIVED

  • Jones HE, Heil SH, Tuten M, Chisolm MS, Foster JM, O'Grady KE, Kaltenbach K. Cigarette smoking in opioid-dependent pregnant women: neonatal and maternal outcomes. Drug Alcohol Depend. 2013 Aug 1;131(3):271-7. doi: 10.1016/j.drugalcdep.2012.11.019. Epub 2012 Dec 29.

    PMID: 23279924DERIVED

  • McNicholas LF, Holbrook AM, O'Grady KE, Jones HE, Coyle MG, Martin PR, Heil SH, Stine SM, Kaltenbach K. Effect of hepatitis C virus status on liver enzymes in opioid-dependent pregnant women maintained on opioid-agonist medication. Addiction. 2012 Nov;107 Suppl 1(0 1):91-7. doi: 10.1111/j.1360-0443.2012.04043.x.

    PMID: 23106931DERIVED

  • Holbrook AM, Baxter JK, Jones HE, Heil SH, Coyle MG, Martin PR, Stine SM, Kaltenbach K. Infections and obstetric outcomes in opioid-dependent pregnant women maintained on methadone or buprenorphine. Addiction. 2012 Nov;107 Suppl 1(Suppl 1):83-90. doi: 10.1111/j.1360-0443.2012.04042.x.

    PMID: 23106930DERIVED

  • Benningfield MM, Dietrich MS, Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Fischer G, Martin PR. Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes. Addiction. 2012 Nov;107 Suppl 1(0 1):74-82. doi: 10.1111/j.1360-0443.2012.04041.x.

    PMID: 23106929DERIVED

  • Coyle MG, Salisbury AL, Lester BM, Jones HE, Lin H, Graf-Rohrmeister K, Fischer G. Neonatal neurobehavior effects following buprenorphine versus methadone exposure. Addiction. 2012 Nov;107 Suppl 1(0 1):63-73. doi: 10.1111/j.1360-0443.2012.04040.x.

    PMID: 23106928DERIVED

  • Gaalema DE, Scott TL, Heil SH, Coyle MG, Kaltenbach K, Badger GJ, Arria AM, Stine SM, Martin PR, Jones HE. Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates. Addiction. 2012 Nov;107 Suppl 1(0 1):53-62. doi: 10.1111/j.1360-0443.2012.04039.x.

    PMID: 23106927DERIVED

  • Kaltenbach K, Holbrook AM, Coyle MG, Heil SH, Salisbury AL, Stine SM, Martin PR, Jones HE. Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction. 2012 Nov;107 Suppl 1(0 1):45-52. doi: 10.1111/j.1360-0443.2012.04038.x.

    PMID: 23106926DERIVED

  • Salisbury AL, Coyle MG, O'Grady KE, Heil SH, Martin PR, Stine SM, Kaltenbach K, Weninger M, Jones HE. Fetal assessment before and after dosing with buprenorphine or methadone. Addiction. 2012 Nov;107 Suppl 1(0 1):36-44. doi: 10.1111/j.1360-0443.2012.04037.x.

    PMID: 23106925DERIVED

  • Jones HE, Fischer G, Heil SH, Kaltenbach K, Martin PR, Coyle MG, Selby P, Stine SM, O'Grady KE, Arria AM. Maternal Opioid Treatment: Human Experimental Research (MOTHER)--approach, issues and lessons learned. Addiction. 2012 Nov;107 Suppl 1(0 1):28-35. doi: 10.1111/j.1360-0443.2012.04036.x.

    PMID: 23106924DERIVED

  • Jones HE, Heil SH, Baewert A, Arria AM, Kaltenbach K, Martin PR, Coyle MG, Selby P, Stine SM, Fischer G. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction. 2012 Nov;107 Suppl 1(0 1):5-27. doi: 10.1111/j.1360-0443.2012.04035.x.

    PMID: 23106923DERIVED

  • Unger A, Jagsch R, Bawert A, Winklbaur B, Rohrmeister K, Martin PR, Coyle M, Fischer G. Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates? Gend Med. 2011 Dec;8(6):355-64. doi: 10.1016/j.genm.2011.10.001. Epub 2011 Nov 15.

    PMID: 22088886DERIVED

  • Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010 Dec 9;363(24):2320-31. doi: 10.1056/NEJMoa1005359.

    PMID: 21142534DERIVED

MeSH Terms

Conditions

Opioid-Related DisordersSubstance-Related DisordersBehavior, Addictive

Interventions

MethadoneBuprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersChemically-Induced DisordersMental DisordersCompulsive BehaviorImpulsive BehaviorBehavior

Intervention Hierarchy (Ancestors)

KetonesOrganic ChemicalsMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Results Point of Contact

Title
Dr. Hendree Jones
Organization
Departments of Psychiatry and Behavioral Sciences and Obstetrics and Gynecology, Johns Hopkins University School of Medicine
hjones18@jhmi.edu
919-485-2664

Study Officials

  • Hendree E. Jones, PhD

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Dept of Psychiatry and Behavioral Sciences

Study Record Dates

First Submitted

December 28, 2005

First Posted

December 30, 2005

Study Start

July 1, 2005

Primary Completion

August 1, 2009

Study Completion

June 1, 2010

Last Updated

August 5, 2015

Results First Posted

August 5, 2015

Record last verified: 2015-07

Locations

CA(1)AU(1)US(6)