Clonidine vs Morphine for Neonatal Abstinence Syndrome

Overseen By Rupinder Kaur, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cooper Health System

Must be taking: NAS medications

Disqualifiers: Premature, Congenital abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 100 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare Clonidine and Morphine to determine if Clonidine, often used to treat high blood pressure, is as effective as Morphine in treating withdrawal symptoms in newborns with Neonatal Abstinence Syndrome (NAS). NAS affects babies whose mothers used certain substances during pregnancy, leading to withdrawal symptoms after birth. The trial seeks to identify which medication more effectively reduces the treatment time for these symptoms. Babies born at or after 35 weeks at Cooper University Hospital, experiencing withdrawal symptoms, and admitted to the NICU or Transitional nursery might be suitable candidates. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What is the safety track record for Clonidine and Morphine Sulfate?

Research has shown that clonidine is generally safe for newborns with Neonatal Abstinence Syndrome (NAS). It effectively serves as a non-opioid treatment with few side effects. However, further studies are needed to determine the optimal dosage for faster results.

Research indicates that morphine sulfate has long been used for NAS treatment and is generally safe when used correctly. However, prolonged use during pregnancy can cause withdrawal symptoms in newborns, which is important to consider.

Both treatments have evidence supporting their safety for newborns with NAS, but they work differently, and the choice depends on individual needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatment for Neonatal Abstinence Syndrome, which typically involves morphine, clonidine offers a unique approach by targeting the central nervous system differently. Clonidine acts on alpha-2 adrenergic receptors to reduce withdrawal symptoms, potentially leading to fewer side effects and a smoother weaning process for newborns. Researchers are excited because clonidine might shorten the duration of treatment compared to morphine, which could mean less time in the hospital for these vulnerable infants.

What evidence suggests that this trial's treatments could be effective for Neonatal Abstinence Syndrome?

This trial will compare Clonidine and Morphine for treating Neonatal Abstinence Syndrome (NAS). Research has shown that Clonidine, one of the treatments in this trial, effectively treats NAS, potentially leading to fewer side effects and shorter hospital stays. Specifically, one study found that adding Clonidine reduced hospital stays by 10 days. Morphine, the other treatment option in this trial, effectively manages withdrawal symptoms in newborns. However, some research suggests that methadone might provide better short-term results than Morphine. Both Clonidine and Morphine have demonstrated benefits, but Clonidine offers a promising non-opioid option. ^{1 2 3 4 5}

Who Is on the Research Team?

Alla Kushnir, MD

Principal Investigator

The Cooper Health System

Are You a Good Fit for This Trial?

This trial is for newborns born at Cooper University Hospital, who are at least 35 weeks gestational age and show withdrawal symptoms from substances their mothers used during pregnancy. These babies should not have congenital anomalies or major medical conditions like blood pressure instability.

Inclusion Criteria

I do not have any birth defects or brain conditions.

I am at least 35 weeks into my pregnancy.

Mothers admitted to using illicit substances or prescription medications (which can result in withdrawal symptoms) while pregnant and/or had a positive urine drug screen during pregnancy

Exclusion Criteria

My blood pressure frequently changes.

Major medical conditions

Infants with major congenital abnormalities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

72 hours to 5 days

In-hospital observation

Treatment

Infants receive either Clonidine or Morphine for NAS treatment, with potential addition of Phenobarbital as rescue therapy

Up to 100 days

Continuous in-hospital monitoring

Follow-up

Participants are monitored for developmental outcomes until 2 years of age

24 months

Contact at 6, 12, and 24 months for ASQ

What Are the Treatments Tested in This Trial?

Interventions

• Clonidine
• Morphine Sulfate

Trial Overview The study compares Clonidine with Morphine Sulfate to see if Clonidine can shorten the hospital stay and treatment duration for Neonatal Abstinence Syndrome (NAS), which affects babies withdrawing from exposure to drugs in the womb.

How Is the Trial Designed?

Group I: Clonidine Experimental Treatment 1 Intervention

Clonidine at 0.38 mcg/kg/dose every 3 hours or 0.5 mcg/kg/dose every 4 hours

Group II: Morphine Active Control 1 Intervention

Morphine Sulfate at 0.03 mg/kg/dose every 3 hours or 0.04 mg/kg/dose every 4 hours

Clonidine is already approved in United States, European Union for the following indications:

Approved in United States as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Approved in European Union as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Who Is Running the Clinical Trial?

The Cooper Health System

Lead Sponsor

Trials

82

Recruited

35,600+

Published Research Related to This Trial

A compounded oral clonidine hydrochloride powder (0.2 mg/g) maintained its stability and quality for 120 days under controlled storage conditions, ensuring consistent dosing for pediatric patients.

No degradation products were detected, and the clonidine content remained within the acceptable range (90.0% to 110.0% of initial content), indicating that the compounded formulation is safe and effective for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. Saito, J., Hanawa, T., Matsumoto, T., et al.[2021]

Clonidine extended-release and clonidine have been found to be effective in treating ADHD symptoms in children and adolescents, based on a review of ten clinical trials, with nine showing positive results.

Both forms of clonidine were reported to be well tolerated, with common side effects including drowsiness and fatigue, but there are concerns about potential serious cardiac side effects, highlighting the need for further research on long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders. Ming, X., Mulvey, M., Mohanty, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6336178/

Evaluation of the Cardiovascular Effects of Clonidine in ... Current literature suggests clonidine is effective for the treatment of NAS and that doses ≤12 mcg/kg per day are tolerated in this neonatal population. Our ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01175668?term=AREA%5BBasicSearch%5D(neonatal%20abstinence%20syndrome)&rank=6

Clonidine for Neonatal Abstinence Syndrome Study Maternal and infant descriptive data will be collected along with specific data regarding vital signs, drug dosages, length of treatment, treatment failures and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26783353/

Role of Clonidine in Neonatal Abstinence Syndrome Limited data suggest that clonidine, in combination with other agents or as monotherapy, may be as effective, with minimal adverse effects and reduced ...

4. publications.aap.org publications.aap.org/pediatrics/article/154/5/e2023065610/199630/Clonidine-as-Monotherapy-for-Neonatal-Opioid

Clonidine as Monotherapy for Neonatal Opioid Withdrawal ... Clonidine appears to be an effective non-opioid medication to treat NOWS. Future studies are needed to determine the optimal clonidine dosage for a quicker ...

5. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.632836/full

A Retrospective Review Following the Addition of ... Results: The implementation of this NAS treatment algorithm significantly reduced the length of hospital stay (30 days vs. 20 days, p = 0.001).