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

• ClinicalTrials.gov Identifier: NCT04547985
• Recruitment Status: Recruiting
• First Posted: September 14, 2020
• Last Update Posted: December 27, 2022
• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prolonged Grief Disorder	Drug: Naltrexone HCl 50 MG Oral Tablet; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Naltrexone Treatment for Prolonged Grief Disorder: A Pilot Study
• Actual Study Start Date: January 5, 2021
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: January 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in Prolonged Grief Disorder symptom severity as assessed by Prolonged Grief-13 (PG-13) [ Time Frame: Weekly for 12 weeks. ]
   Change in PGD symptom severity will be measured by using Prolonged Grief-13 (PG-13), a self-rated scale consisting of 11 items. For this study, we have added an additional item inquiring about loneliness to be congruent with DSM 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 PG-13 was tested and validated in previous studies.
2. Change in Prolonged Grief Disorder severity as assessed by Structured Clinical Interview for PGD (SCIP) [ Time Frame: Every 4 weeks for 8 weeks ]
   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.

Secondary Outcome Measures :

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 [ Time Frame: Every 4 weeks for 12 weeks ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Francesco Osso; 929-578-0305; fro4001@med.cornell.edu

Contact: Hillary Winoker; 646-962-7143; hiw4002@med.cornell.edu

Locations

United States, New York

Weill Cornell Medicine; Recruiting

New York, New York, United States, 10021

Contact: Holly G Prigerson, PhD 617-459-3304 hgp2001@med.cornell.edu

Sponsors and Collaborators

Weill Medical College of Cornell University

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Holly G Prigerson, PhD; Weill Medical College of Cornell University

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04547985
• Other Study ID Numbers: 20-04021873; 5R35CA197730-05 ( U.S. NIH Grant/Contract )
• First Posted: September 14, 2020
• Last Update Posted: December 27, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Weill Medical College of Cornell University:

Naltrexone

Additional relevant MeSH terms:

Disease; Pathologic Processes; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents