Naltrexone for Prolonged Grief Disorder

NCT06140420 | Terminated Phase 4 FDA Drug

• 1 other identifier: TexasTechU6
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Naltrexone HCl 50 MG Oral Tablet; Placebo

Outcome Measures

Primary Outcomes (2)

• Change in Prolonged Grief Disorder symptom severity as assessed by the PGD-12

  Change in PGD symptom severity will be measured by using Prolonged Grief-13 (PGD-12), a self-rated scale consisting of 12 items. For this study, we have added an additional item inquiring about loneliness to be congruent with DSM-5-TR criteria and SCIP. This 5-point Likert-type of measurement tool evaluates the intensity and severity of the PGD. The validity and reliability of the PGD-12 was tested and validated in previous studies.

  Weekly for 12 weeks

• Change in Prolonged Grief Disorder severity as assessed by Structured Clinical Interview for PGD

  The IOS is a self-reported pictorial tool use to measure the subjectively perceived closeness of a relationship. The tool asks respondents to select one of seven pairs of increasingly overlapping circles that best represents their relationship with another, with more overlap signifying a closer relationship. This scale possesses good reliability, with (α = .93) for the entire sample, (α = .87) for family, (α = .92) for friendship, and (α = .95) for romantic relationships. Test-retest reliability shows similar findings, with (α = .83) for the entire sample, (α = .85) for family, (α = .86) for friendship, and (α = .85) for romantic relationships.

  Every 4 weeks for 8 weeks

Secondary Outcomes (1)

• Change in strength of subjectively perceived closeness of a social relationship as measured by the Inclusion of the other in the Self (IOS) Scale

  Every 4 weeks for 12 weeks

Study Arms (2)

Placebo Comparator: Placebo

PLACEBO COMPARATOR

24 randomized patients will take placebo daily for 8 weeks.

Drug: Placebo

Active Comparator: Naltrexone

ACTIVE COMPARATOR

24 randomized patients will take naltrexone daily for 8 weeks

Drug: Naltrexone Oral Product

Interventions

Naltrexone Oral Product DRUG

Generic, oral tablet.

Active Comparator: Naltrexone

Placebo DRUG

Oral Placebo

Placebo Comparator: Placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Lives within a reasonable distance from NYPH for convenient clinic visits.
• Can speak, read, and write English proficiently.
• Meet diagnostic criteria for PGD based on the DSM guidelines
• If a female patient, must agree to use a method of contraception and be willing and able to continue contraception during the first 8 weeks of the study while she is taking the study drug. Female patients who are planning to use oral hormonal contraception during this time must have initiated it at least 2 months prior to the baseline visit.
• If a male patient, must agree to use a method of contraception and be willing and able to continue contraception during the first 8 weeks of the study while he is taking the study drug.

You may not qualify if:

• Having recently started taking/prescribed medications for any psychiatric illness (e.g.
• SSRIs for MDD) within the past 3 months; participants who have been taking this medication for longer than 3 months can be included.
• Having recently started psychotherapy for any psychiatric illness within the past 3 months; participants who have been receiving psychotherapy for longer than 3 months can be included.
• Prior history of recently active (e.g. within the past 3 months) opioid dependence.
• Current prescription, non-prescription, or illicit opioid use, (i.e., acute use within the past 14 days or chronic use within the last 30 days), including opioid antagonists for alcohol or opioid dependence, all opioid analgesics, certain cough and cold remedies (e.g., codeine), and certain anti-diarrheal preparations (e.g., loperamide).
• Possible future use of opioids during the study (e.g. for surgery).
• Current use of leflunomide (Arava), droperidol (Droleptan), diazepam (Valium), thioridazine (Mellaril, Novoridazine, Thioril), or any other clinically relevant medication that has potential to cause liver injury with concurrent use of naltrexone.
• Currently pregnant, lactating, or planning to become pregnant during the study.
• Active hepatitis or liver disease.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than one standard deviation (SD) above the upper limit of normal on initial laboratory examination. Screen positive for active suicidal thoughts or behaviors.

Sponsors & Collaborators

• Texas Tech University: lead
• Texas Tech University Health Science Center: collaborator

Study Sites (1)

Texas Tech Health Science Center

Lubbock, Texas, 79409, United States

Location

Related Publications (2)

• Gang J, Kocsis J, Avery J, Maciejewski PK, Prigerson HG. Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial. Trials. 2021 Feb 1;22(1):110. doi: 10.1186/s13063-021-05044-8.

  PMID: 33522931 BACKGROUND

• Kakarala SE, Roberts KE, Rogers M, Coats T, Falzarano F, Gang J, Chilov M, Avery J, Maciejewski PK, Lichtenthal WG, Prigerson HG. The neurobiological reward system in Prolonged Grief Disorder (PGD): A systematic review. Psychiatry Res Neuroimaging. 2020 Sep 30;303:111135. doi: 10.1016/j.pscychresns.2020.111135. Epub 2020 Jul 3.

  PMID: 32629197 BACKGROUND

Study Design

• Study Type: interventional
• Phase: phase 4
• 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: Assistant Professor

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 20, 2023
• Study Start: August 1, 2023
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)