Naltrexone for Prolonged Grief Disorder

(NPGD Trial)

Overseen By Yasin Ibrahim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Texas Tech University

Must not be taking: Opioids, Leflunomide, Diazepam, others

Disqualifiers: Opioid dependence, Liver disease, others

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: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of naltrexone for individuals with prolonged grief disorder (PGD), characterized by intense and persistent grief that disrupts daily life. Participants will take either naltrexone or a placebo for eight weeks to determine its impact on symptoms like sadness and social connections. Ideal candidates are those managing PGD who have not started new medications or therapies for any psychiatric condition in the past three months. As a Phase 4 trial, this research seeks to understand how this FDA-approved treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you have recently started psychiatric medications or psychotherapy within the past 3 months, or if you are currently using opioids or certain other medications that may interact with naltrexone.

What is the safety track record for naltrexone?

Research has shown that naltrexone is generally safe and well-tolerated in people. The FDA has approved naltrexone for treating alcohol and opioid dependence, confirming its safety for these uses.

For treating prolonged grief disorder (PGD), some psychiatrists have observed that naltrexone might alleviate grief symptoms. However, specific safety information for its use in PGD remains limited. Studies on its use for this condition have not reported any major side effects.

In summary, while more research is needed to fully understand its safety for PGD, existing data from its use in other conditions is reassuring. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for Prolonged Grief Disorder that often involve psychotherapy or antidepressants, naltrexone offers a unique approach by targeting the brain's opioid receptors. This is exciting because naltrexone, commonly used to treat addiction, may address the biological underpinnings of grief by altering how the brain processes emotional pain. Researchers are hopeful that this novel mechanism could provide faster and more effective relief for those struggling with prolonged grief, offering a new avenue beyond traditional therapy and medication methods.

What evidence suggests that naltrexone might be an effective treatment for prolonged grief disorder?

Research has shown that naltrexone, which participants in this trial may receive, can help reduce symptoms of prolonged grief disorder (PGD) to some extent. Studies have found that it can ease grief symptoms, though results may vary due to other mental health issues in participants. Already approved for treating other conditions, naltrexone shows promise for PGD. However, evidence specifically for PGD is still developing, and further research is needed to confirm its effectiveness for this condition. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults who live near NYPH, can communicate in English, and have been diagnosed with prolonged grief disorder. They must be willing to use contraception and not start any new psychiatric meds or therapy within the last 3 months. People using opioids, certain medications that affect the liver, or those with active hepatitis or abnormal liver tests cannot join.

Inclusion Criteria

You can speak, read, and write English well.

You have been diagnosed with PGD according to the DSM guidelines.

I am using or will use birth control during and 8 weeks after the study.

Exclusion Criteria

I started psychotherapy for a mental health issue more than 3 months ago.

I might need opioids for pain during the study.

I have active hepatitis or another liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either naltrexone or placebo daily for 8 weeks

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone

Trial Overview The study is testing if oral naltrexone helps people with prolonged grief disorder over an 8-week period compared to a placebo. Participants will visit monthly for symptom checks and monitoring of social connections and side effects.

How Is the Trial Designed?

Group I: Active Comparator: Naltrexone Active Control 1 Intervention

24 randomized patients will take naltrexone daily for 8 weeks

Group II: Placebo Comparator: Placebo Placebo Group 1 Intervention

24 randomized patients will take placebo daily for 8 weeks.

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

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

Texas Tech University

Lead Sponsor

Trials

89

Recruited

10,300+

Texas Tech University Health Science Center

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

A systematic review of 49 trials found that only 14% of studies on naltrexone for alcohol dependence had high adherence assurance, which may explain the variability in treatment efficacy observed.

The study revealed a significant correlation between adherence levels and treatment outcomes, suggesting that improving adherence monitoring could enhance the effectiveness of naltrexone in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. Swift, R., Oslin, DW., Alexander, M., et al.[2022]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

Extended-release naltrexone (XR-NTX) has been shown to significantly increase both initial and 6-month abstinence in alcohol-dependent adults, particularly those who have achieved at least 4 days of initial abstinence.

In opioid dependence, XR-NTX effectively maintains abstinence, reduces cravings, and prevents relapse after detoxification, demonstrating its potential as a valuable treatment option in both primary care and public health systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular extended-release naltrexone: current evidence. Gastfriend, DR.[2022]

A population pharmacokinetic analysis of 453 subjects showed that the clearance and distribution of naltrexone, used for alcohol dependence, are influenced by factors like weight and age, but these differences are not clinically significant enough to require dosage adjustments.

The study found that naltrexone clearance was higher in individuals with alcohol and/or opioid dependence compared to healthy subjects, indicating that while there are variations in pharmacokinetics, standard dosing of XR-NTX remains appropriate across different subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. Dunbar, JL., Turncliff, RZ., Hayes, SC., et al.[2019]

Induction success for extended-release naltrexone (XR-NTX) is significantly lower in individuals requiring opioid detoxification (62.6%) compared to those already detoxified (85.0%), indicating that detoxification status is crucial for treatment initiation.

Adherence to XR-NTX is relatively low, with only 44.2% of individuals completing all scheduled injections, and adherence rates are notably higher in controlled research settings compared to routine care, which limits the overall effectiveness of XR-NTX in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. Jarvis, BP., Holtyn, AF., Subramaniam, S., et al.[2019]

A review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

A pilot study involving 30 alcohol-dependent patients showed that the long-acting injectable naltrexone (Vivitrex) is generally safe and well tolerated, with mild to moderate adverse events that resolved without intervention.

The study confirmed that therapeutic levels of naltrexone were maintained throughout the 4-month treatment period, suggesting that this formulation could improve patient adherence by eliminating the need for daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. Johnson, BA., Ait-Daoud, N., Aubin, HJ., et al.[2019]

This study is the first to explore the use of oral naltrexone, a medication typically used for addiction treatment, as a potential pharmacological therapy for Prolonged Grief Disorder (PGD) in 48 participants over an 8-week period.

The researchers hypothesize that naltrexone will significantly reduce PGD symptoms compared to a placebo, addressing the urgent need for effective treatments for this debilitating condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial. Gang, J., Kocsis, J., Avery, J., et al.[2021]

Citations

1. psychiatrist.com psychiatrist.com/pcc/complicated-grief-role-naltrexone/

Complicated Grief: Is There a Role for Naltrexone? Data from randomized controlled trials show that grief-focused cognitive-behavioral therapy (CBT) effectively reduces PGD symptoms, providing ...

2. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05044-8

Naltrexone treatment for prolonged grief disorder - Trials While these studies demonstrate moderate effectiveness in reducing grief symptoms, the results are confounded by high rates of comorbid mental ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7848251/

Naltrexone treatment for prolonged grief disorder While these studies demonstrate moderate effectiveness in reducing grief symptoms, the results ... efficacy, and adverse event data for all enrolled subjects.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04547985

Naltrexone Treatment for Prolonged Grief Disorder (PGD) This is a study to see how effective oral naltrexone is as treatment for prolonged grief disorder (PGD). Participants will take their assigned medication ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1064748123004694

Prolonged Grief Disorder: Addressing Misconceptions With ... We present data demonstrating that PGD is a diagnosis that applies to a rare few mourners who are at risk of significant distress and dysfunction.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12210328/

Prolonged Grief Disorder: Data-Driven Corrections of ... Based on anecdotal evidence from psychiatrists in Boston and Sao Paolo, naltrexone appeared to losen the grip of grief and permit those with PGD ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06140420

NCT06140420 | Naltrexone for Prolonged Grief Disorder In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...