Naltrexone for Prolonged Grief Disorder

Study Overview
=================
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.

Official Title
-----------------
Naltrexone Treatment for Prolonged Grief Disorder: A Proof of Concept Study

Conditions
-----------------
Naltrexone HCl 50 MG Oral Tablet, Placebo

Intervention / Treatment
-----------------
* Drug: Naltrexone Oral Product
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 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. Exclusion Criteria: • 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator: Placebo<br>24 randomized patients will take placebo daily for 8 weeks. | Drug: Placebo<br>* Oral Placebo<br>|
| Active Comparator: Active Comparator: Naltrexone<br>24 randomized patients will take naltrexone daily for 8 weeks | Drug: Naltrexone Oral Product<br>* Generic, oral tablet.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 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 12 weeks |