Low Dose Naltrexone (LDN) Immune Monitoring

Study Overview
=================
Brief Summary
-----------------
We have found that low dose naltrexone (LDN) can substantially reduce pain associated with fibromyalgia syndrome. We believe LDN may work via novel anti-inflammatory channels. The purpose of this study is to determine if LDN lowers inflammatory markers in individuals with fibromyalgia.

Detailed Description
-----------------
Eligible women with Fibromyalgia (FM) will be enrolled into a 10-week drug trial. During the first two weeks, a baseline phase will be used to collect data on immune function and symptoms. LDN will be administered for 8 weeks. Although there is no placebo arm built-in, participants will be advised that they may receive a placebo during the trial. Participants will provide twice daily symptom reports using an android tablet device and Dooblo SurveyToGo survey software. Participants will also provide a blood sample twice every week for the duration of the study. Plasma inflammatory markers will be tested using a luminex based 63-plex inflammatory assay panel. The primary aim of the study is to test if 8 weeks of LDN administration is associated with a reduction in pro-inflammatory markers in plasma in women with FM.

Official Title
-----------------
Low Dose Naltrexone (LDN) Immune Monitoring

Conditions
-----------------
Fibromyalgia

Intervention / Treatment
-----------------
* Drug: Low Dose Naltrexone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females age 18-65 Meets criteria for 1990 ACR criteria for fibromyalgia Able to receive venous blood draw twice a week for 16 weeks Sufficient symptom variability during baseline report Patient completes daily report during 2 week baseline period at least 80% completion rate. Exclusion Criteria: Opioid use Significant psychological comorbidity that in the discretion of the investigator compromises study integrity Location prohibits travel to Stanford Blood or clotting disorder Rheumatologic or autoimmune disease Acute infection Baseline blood ESR >60, CRP greater than 3.0mg/L, positive rheumatoid factor, or positive ANA Use of blood thinning medication Pregnant or currently planning to become pregnant Current use of aspirin, ibuprofen, naproxen, or other confounding-anti-inflammatory medication as part of regular medication regimen. Known allergy to Naltrexone or Naloxone Currently participating in another treatment-based research study Self-reported inability to refrain from alcohol for the duration of the study period

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low Dose Naltrexone (LDN)<br>Following a two-week baseline the study drug was administered daily for 8 weeks. Participants were informed that placebo or LDN would be provided during the drug period and that all participants would receive LDN at some point during the study. In fact, all participants received the active LDN (4.5 mg nocte) throughout the drug-administration period. | Drug: Low Dose Naltrexone<br>* Naltrexone 4.5 mg p.o. nocte<br>* Other names: Naltrexone;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-7 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-8 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-9 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-10 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-12p40 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-12p70 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-13 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-15 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-17A From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-17F From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-18 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-21 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-23 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-31 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-27 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in LIF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in G-CSF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in GM-CSF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in MIP-1α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in SDF-1α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IP-10 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in Eotaxin From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in RANTES From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in MIP-1β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in MCP-1 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in MCP-3 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in MIG From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in TRAIL From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in CD40L From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in TGF-α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in TGF-β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IFN-α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IFN-β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IFN-γ From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in TNF-α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in TNF-β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in PIGF-1 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in SCF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in HGF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in VEGF-D From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in VEGF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in NGF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in EGF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in FGF-β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in M-CSF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in BDNF From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in ICAM-1 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in VCAM-1 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in ENA-78 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in PDGF-BB From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in PAI-1 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in Leptin From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in Resistin From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in GROa From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in FaSL From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-22 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in Pain From Baseline. | Visual analog scale (0-100) anchored at no pain at 0 and worst possible pain at 100. Improvement in pain would be indicated by a decrease in the score. | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in Overall Fibromyalgia Symptoms From Baseline. | Visual analog scale (0-100) anchored at no symptoms at 0 and worst possible symptoms at 100. Improvement in overall fibromyalgia symptoms would be indicated by a decrease in the score. | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-1α From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-1β From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-1Ra From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-2 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-4 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-5 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. | 
| Change in IL-6 From Baseline. |  | Baseline period (2 weeks) through end of drug phase (8 weeks) [10 weeks total]. |