Naltrexone Treatment for Prolonged Grief Disorder (PGD) (PGD)

Naltrexone Treatment for Prolonged Grief Disorder: A Pilot Study

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.

Study Overview

• Status: Terminated
• Conditions: Prolonged Grief Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Naltrexone HCl 50 MG Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age or older.
2. Lives within a reasonable distance from NYPH for convenient clinic visits.
3. Can speak, read, and write English proficiently.
4. Meet diagnostic criteria for PGD based on the DSM guidelines
5. 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.
6. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Prior history of recently active (e.g. within the past 3 months) opioid dependence.
4. 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).
5. Possible future use of opioids during the study (e.g. for surgery).
6. 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.
7. Currently pregnant, lactating, or planning to become pregnant during the study.
8. Active hepatitis or liver disease.
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than one standard deviation (SD) above the upper limit of normal on initial laboratory examination.
10. Screen positive for active suicidal thoughts or behaviors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 24 randomized patients will take placebo daily for 8 weeks.	Drug: Placebo; Composed of filler material and encapsulated to appear identical to naltrexone.
Active Comparator: Naltrexone; 24 randomized patients will take naltrexone daily for 8 weeks	Drug: Naltrexone HCl 50 MG Oral Tablet; Generic, oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Prolonged Grief Disorder Symptom Severity as Assessed by Prolonged Grief-13 (PG-13)	Prolonged Grief Disorder (PGD) is a newly defined syndrome that is a specific reaction to the loss of a loved one. Change in PGD symptom severity will be measured by using Prolonged Grief-13-R (PG-13-R), a self-rated scale consisting of 11 items. The validity and reliability of the scale were tested and validated in previous studies. Minimum Score: 11 - reflecting the lowest level of PGD symptom severity (distress) Maximum Score: 55 - reflecting the highest level of PGD symptom severity (distress) Diagnostic Criteria PGD symptom severity of ≥30 is the threshold for "syndromal" level PGD. Prolonged Grief (PG-13-R) is a diagnostic tool. If a respondent meets the diagnostic criteria for PGD, this suggests that they should seek more thorough evaluation from a mental health professional. Only an in-person assessment by a mental health professional can determine for certain the clinical significance of the reported symptoms, and provide recommendations or referrals for treatment.	Baseline and 8 Weeks
Change in Prolonged Grief Disorder Symptom Severity as Assessed by Prolonged Grief-13	Prolonged Grief Disorder (PGD) is a newly defined syndrome that is a specific reaction to the loss of a loved one. Change in PGD symptom severity will be measured by using Prolonged Grief-13-R (PG-13-R), a self-rated scale consisting of 11 items. The validity and reliability of the scale were tested and validated in previous studies. Minimum Score: 11 - reflecting the lowest level of PGD symptom severity (distress) Maximum Score: 55 - reflecting the highest level of PGD symptom severity (distress) Diagnostic Criteria PGD symptom severity of ≥30 is the threshold for "syndromal" level PGD. Prolonged Grief (PG-13-R) is a diagnostic tool. If a respondent meets the diagnostic criteria for PGD, this suggests that they should seek more thorough evaluation from a mental health professional. Only an in-person assessment by a mental health professional can determine for certain the clinical significance of the reported symptoms, and provide recommendations or referrals for treatment.	Baseline and 12 weeks
Change in Number of Participants With Prolonged Grief Disorder as Assessed by Structured Clinical Interview for PGD (SCIP)	Eligibility for the study and change in symptom severity will be measured by SCIP. This structured clinical interview is adapted to the DSM-5-TR criteria for PGD. Interviewers will be trained to standard which will be a κ > 0.8 agreement between trainee and trainer.	Every 4 weeks for 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Strength of Subjectively Perceived Closeness of a Social Relationship as Measured by the Inclusion of the Other in the Self (IOS) Scale	The Inclusion of Other in the Self (IOS) Scale is a self-reported pictorial tool used to measure the subjectively perceived closeness of a relationship. Respondents choose a pair of seven circles with different degrees of overlap. 1=no overlap; 2=little overlap; 3=some overlap; 4=equal overlap; 5=strong overlap; 6=very strong overlap; 7=most overlap. The tool asks respondents to select one of seven pairs of increasingly overlapping circles that best represent 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. Minimum Score: 1 - reflecting the least amount of overlap Maximum Score: 7 - reflecting the most amount of overlap	Every 4 weeks for 12 weeks

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Holly G Prigerson, PhD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): October 16, 2023
• Study Completion (Actual): October 16, 2023

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Naltrexone
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Prolonged Grief Disorder; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 20-04021873; 5R35CA197730-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No