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

7 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug naltrexone for treating prolonged grief disorder?

Naltrexone is currently used to treat alcohol and opioid dependence, and it works by affecting the brain's reward pathway, which is thought to be involved in prolonged grief disorder. This suggests that naltrexone might help reduce symptoms of prolonged grief disorder by targeting similar brain circuits. ^{1 2 3 4 5}

Is naltrexone safe for humans?

Naltrexone, used for treating alcohol and opioid dependence, has been studied for safety in humans. Injectable extended-release naltrexone (Vivitrol) has been evaluated for long-term safety in opioid dependence, and oral naltrexone is considered safe and convenient for use in prolonged grief disorder. ^{1 2 4 6 7}

How is the drug naltrexone unique for treating prolonged grief disorder?

Naltrexone is unique for treating prolonged grief disorder because it targets the brain's reward pathway, similar to how it treats addiction, which is a novel approach for this condition. Unlike other treatments, it is used in an oral form for its safety and convenience, and there are currently no standard pharmacological treatments for prolonged grief disorder. ^{1 2 3 5 8}

What is the purpose of this trial?

This is a study to see how effective oral naltrexone is as treatment for prolonged grief disorder (PGD). Participants will take their assigned medication for 8 weeks, with monthly visits to assess symptom severity, social connectedness, and adverse reactions.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Extended-release injectable naltrexone for opioid use disorder: a systematic review. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. [2019]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. [2016]

8. England 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. [2019]