AzTrials
AzTrials

SpasticityPhase 1/2Best PK/PDNCT00607542

Oral Baclofen Pharmacokinetics and Pharmacodynamics in Children With Spasticity

A Phase 1/2 study testing baclofen in people with Spasticity and Cerebral Palsy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Oral baclofen is used commonly to treat spasticity in children with cerebral palsy. Although for adults there is dosing,safety and efficacy information in the package insert, this is not the case for children. Read more about this study

Who is it for?
Ages 2 to 16 years
Conditions the study is for
Spasticity, Cerebral Palsy
What is being tested?
baclofen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
11 sitesUnited States
Study dates
Nov 2008to Jan 2011
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Males and females aged 2-16 years, inclusive.
  • Triceps skinfold thickness between the 5th and 95th percentiles for age (Refer to Appendix 3).
  • Gross Motor Function Classification Scale (GMFCS) Level II - V (GMFCS classifies children by functional mobility with Level I indicating minimal motor disability and V indicating total body involvement and dependence on others for mobility (Palisano et al, 1997).
  • Ashworth score of 2 or higher in at least one arm and one leg (knee + elbow flexors and/or extensors).
  • Cerebral Palsy: Motor disability due to a static, non-progressive brain injury/ malformation occurring prenatally or any time prior to the age of 2 years.
  • No history of baclofen use within the past 4 months.
  • Female subject, is premenarchal, or is incapable of pregnancy because of a hysterectomy or tubal ligation; or female subject who is sexually active and capable of pregnancy, has been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier) for at least one month prior to study entry and agrees to continue to use one of these for the duration of the study; or female subject who is sexually abstinent and capable of pregnancy, agrees to continued abstinence or to use an acceptable method of birth control (either intrauterine device or spermicide and barrier) should sexual activity commence.
  • Subject ≥10 years of age has negative urine tests at screening and baseline for alcohol, non-medically prescribed drugs of abuse, and no history of tobacco use.

Who cannot join

  • Hypersensitivity to baclofen.
  • Selective dorsal rhizotomy.
  • Active intrathecal baclofen pump within the past 6 months.
  • Use of botulinum toxin in past 4 months or use any time during the study.
  • Use of tone altering medications (e.g. baclofen, benzodiazepines, levodopa, trihexyphenidyl) for >3 consecutive days duration within the past 4 months.
  • Start of any drug or product known to be a significant cytochrome P450 enzyme inducer or inhibitor within the past 30 days.
Show all 24Show fewer
  • Orthopaedic surgery within the past year or any time during the study.
  • Abdominal surgery within the past six months or any time during the study.
  • Uncontrolled seizures (baseline seizure frequency >1 per month or history of more than 2 prolonged seizures lasting longer than 5 minutes duration within the past year.
  • Severe behavior difficulties or psychiatric disturbance
  • Proven gastric dysmotility: known history of abnormal gastric emptying study and/or history of vomiting 3 or more times per week.
  • Severe Gastroesophageal Reflux Disease: known history of esophagitis (documented on abnormal endoscopy or biopsy).
  • Malnutrition: defined as triceps skin fold thickness less than 5th or greater than 95th percentile for age.
  • Renal or Liver disease: Elevated bilirubin, LFTs greater than twice the upper limit of normal, reduced BUN/Cr ratio (<5), or abnormal creatinine clearance that is clinically significant as determined by the investigator.
  • Abnormal CBC: Anemia, polycythemia, neutropenia, leukocytosis, thrombocytopenia, or thrombocytosis clinically significant as determined by the investigator.
  • Pregnancy or lactation.
  • Severe respiratory or cardiac disease: Requirement for prolonged supplemental oxygen (>7 days), history of clinically significant congenital heart disease, congestive heart failure or cardiomegaly, and/or hospital admission within past 6 months for cardiac symptoms or respiratory distress.
  • Previous baclofen failure: Lack of response to baclofen or presence of unacceptable side effects. If previous baclofen therapy was tried >4 months prior to study and discontinued, the decision to enroll subject will be at the discretion of the site investigator and reason for discontinuation of oral baclofen will be recorded.
  • Use of medications that interfere with measurements of serum creatinine levels within the past 14 days (e.g., trimethoprim-sulfa, fibric acid derivatives other than gemfibrizol, keto acids, salicylates, some cephalosporins, cimetidine, phenacemide) .
  • Subject tests positive at screening for the hepatitis B surface antigen or hepatitis C antibody, or has a history of a positive result for one of these tests.
  • Subject is known to have tested seropositive for the human immunodeficiency virus (HIV) or subject is concomitantly receiving anti-retroviral therapy.
  • Any serious, unstable medical illness or clinically significant abnormal laboratory assessment that would adversely impact the scientific interpretability or unduly increase the risks of the protocol.
  • Subject has a disorder or history of a condition, other than that related to CP that could interfere with drug absorption, distribution, metabolism, or excretion.
  • Any condition which would make the patient

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Kennedy Krieger Institute

    Baltimore, Maryland, 21205

  • Kluge Children's Rehabilitation Center - University of Virginia

    Charlottesville, Virginia, 22903

  • Rehabilitation Institute of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Mercy Hospital and Clinics

    Kansas City, Missouri, 64108

  • Children's Hospital of Lousiana

    New Orleans, Louisiana, 70118

  • Gillette Children's Speciality Healthcare

    Saint Paul, Minnesota, 55101

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington Univeristy - St. Louis Children's hospital

    St Louis, Missouri, 63110-1093

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

Other trials in United States

About this study

Official title: Pediatric Pharmacokinetic and Pharmacodynamic Study of Oral Baclofen for the Treatment of Spasticity Associated With Cerebral Palsy

Oral baclofen is used commonly to treat spasticity in children with cerebral palsy. Although for adults there is dosing,safety and efficacy information in the package insert, this is not the case for children. The purpose of this study is to determine how fast the drug is cleared from the body, the correct dose, and long-term safety and efficacy for children with spasticity.

Read the detailed description

Although oral baclofen has been used for several decades for the treatment of spasticity in adults and in children, there is very little data regarding the pharmacokinetic (PK) or pharmacodynamic (PD) properties of baclofen in children. Therefore, pediatric guidelines, including dose ranges, dosing schedules, dose escalation strategies and anticipated side effects are extrapolated from adult data and require an assumption that safety and efficacy in children is comparable to that in adults. Furthermore, there is wide variability in dosing strategies among practitioners who treat children with cerebral palsy (CP) with respect to starting doses, maximum doses and rates of dose escalation.Establishment of safe and effective dosing strategies for children with CP requires an understanding of the PK and PD properties of baclofen in children and recognition of individual differences that may contribute to divergent clinical responses to baclofen among children with CP.

Being tested
baclofen
Keywords
spasticity, cerebral palsy, baclofen, pharmacokinetics, pharmacodynamics, dosing, safety, efficacy
Medical subject headings
Muscle Spasticity, Cerebral Palsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • baclofenDrug

    Also called Lioresal

    2.5 mg oral baclofen tablets given three times a day; dose gradually escalated as specified in the protocol

Study groups in NCT00607542
Study groupRoleWhat they receive
1Active comparatorstarting dose of baclofen 2.5 mg PO TID with dose escalation as tolerated
Receives: Drug: baclofen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine pharmacokinetic parameters of oral baclofen in children with spasticity associated with cerebral palsy (CP).

    Measured: 1 year

  2. Describe the relationship between plasma concentrations of oral baclofen and clinical measures of spasticity.

    Measured: 1 year

  3. Determine optimal dosing range and interval for administration of oral baclofen for use in a randomized clinical trial of safety and efficacy.

    Measured: 1 year

Secondary outcomes (3)

  1. Describe the relationship between plasma concentrations of oral baclofen and measures of strength, function, ease of care, pain/comfort and health related quality of life.

    Measured: 1 year

  2. Describe the safety and tolerability of oral baclofen in children with spasticity associated with CP.

    Measured: 1 year

  3. Investigate preliminarily whether oral baclofen improves dystonia

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionJan 2011
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00607542
Sponsor's protocol ID
NICHD-2005-13-2
Other IDs
267200603421
Acronym
Best PK/PD
Status last verified
Feb 2011
First submitted
22 Jan 2008
Last updated
6 Dec 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • McLaughlin MJ, He Y, Brunstrom-Hernandez J, Thio LL, Carleton BC, Ross CJD, Gaedigk A, Lewandowski A, Dai H, Jusko WJ, Leeder JS. Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy. PM R. 2018 Mar;10(3):235-243. doi: 10.1016/j.pmrj.2017.08.441. Epub 2017 Sep 1.

    PubMed 28867665

  • He Y, Brunstrom-Hernandez JE, Thio LL, Lackey S, Gaebler-Spira D, Kuroda MM, Stashinko E, Hoon AH Jr, Vargus-Adams J, Stevenson RD, Lowenhaupt S, McLaughlin JF, Christensen A, Dosa NP, Butler M, Schwabe A, Lopez C, Roge D, Kennedy D, Tilton A, Krach LE, Lewandowski A, Dai H, Gaedigk A, Leeder JS, Jusko WJ. Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy. J Pediatr. 2014 May;164(5):1181-1188.e8. doi: 10.1016/j.jpeds.2014.01.029. Epub 2014 Mar 5.

    PubMed 24607242

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing baclofen in people with Spasticity and Cerebral Palsy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine pharmacokinetic parameters of oral baclofen in children with spasticity associated with cerebral palsy (CP). (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00607542, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2011.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in