Pomegranate Juice Consumption by Patients Under Medication for Addiction Treatment as a Regulator of Craving and Blood Redox Status: The Study Protocol of a Randomized Control Trial (the NUTRIDOPE Study)
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Craving
Study Overview
Brief Summary
The NUTRIDOPE (NUTRItion-driven Detoxification of OPioid addicted patiEnts) study is a clinical trial that aims to investigate the role of pomegranate juice consumption by opioid-addicted patients under buprenorphine and methadone on craving, which is the primary outcome, and other parameters. In detail, fresh pomegranate juice will be administered for 120 days (250 ml, 7 days/week) to the patients and craving as well as other psychosocial (e.g., depression, mood state, quality of life) and biochemical (i.e., blood redox status and inflammation) parameters will be evaluated. It is hypothesized that pomegranate juice will reduce craving probably through the improvement of blood redox and inflammation status.
Pomegranate juice, which is the examined nutritional intervention, will be administered to the participants of the experimental group, whereas their counterparts in the control group will not consume any similar beverage as a placebo due to the objective difficulties of making one that will be identical and not separable with the fresh pomegranate juice.
Detailed Description
Background: Buprenorphine and methadone are considered the "gold standard" medication for addiction treatment (MAT) for patients with opioid use disorders (OUDs). However, they may cause side effects promoting craving (i.e., opioid use relapse). Therefore, the concurrent administration of natural products could be an adjunct intervention to back up opioid MAT. Pomegranate is a natural substance that contains antioxidant polyphenolic compounds, which have been associated with craving reduction. Moreover, pomegranate positively affects psychosocial parameters, such as depression and anxiety that are common feelings for patients with OUDs, probably due to its potent antioxidant and anti-inflammatory properties.
Objectives: The NUTRIDOPE (NUTRItion-driven Detoxification of OPioid addicted patiEnts) study aims to investigate the role of pomegranate juice consumption by patients with OUDs under buprenorphine and methadone on craving.
Methods: Fresh pomegranate juice will be administered for 120 days (250 ml, 7 days/week) and craving, as the primary outcome, as well as other psychosocial (e.g., depression, mood state, quality of life) and biochemical (i.e., blood redox status and inflammation) parameters will be evaluated.
Anticipated Results: It is hypothesized that pomegranate juice will reduce craving probably through the improvement of blood redox and inflammation status.
Conclusions: NUTRIDOPE is a hypothesis-driven, evidence-based, multifactorial project that proposes a nutrition-based solution towards craving reduction for patients with OUDs under MAT, potentially assisting towards their successful rehab and societal reintegration.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Over 20 years of age
- •Long-term heroin or other opioid drug use
- •Suffering from physical and mental dependence due to chronic opioid use
Exclusion Criteria
- •Serious medical problems, such as infection by human immunodeficiency virus or hepatitis B virus
- •Current use of anti-inflammatory medication
- •Relapse to other addictive substances (i.e., opioids, methamphetamine, benzodiazepines, cannabis, tetrahydrocannabinol, amphetamine) - To rule out the use of such substances, all participants underwent weekly urine tests during the four-month period of the experiment
Arms & Interventions
Experimental group
Patients under medication for addiction treatment (MAT) that are active members of the Greek Organization Against Drugs (OKANA) therapeutic units will be recruited for this investigation. The participants will be stratified into two subgroups, i.e., methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT), according to the maintenance treatment program they attend. Pomegranate juice, which is the examined nutritional intervention, will be administered to the participants of both MMT and BMT subgroups of the experimental group. The juice will be administered to the patients at the following dosage: 250 ml/day, seven days/week, for four months.
Intervention: Pomegranate juice (Dietary Supplement)
Control group
Patients under medication for addiction treatment (MAT) that are active members of the Greek Organization Against Drugs (OKANA) therapeutic units under methadone or buprenorphine treatment. The participants will be stratified into two subgroups, i.e., methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT), according to the maintenance treatment program they attend. The patients of the control group (both MMT and BMT subgroups) will not consume any similar beverage as a placebo due to the objective difficulties of making one that will be identical to the fresh pomegranate juice.
Outcomes
Primary Outcomes
Craving
Time Frame: Changes between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement) will be assessed.
Heroin Craving Questionnaire (HCQ), which is a validated instrument, will be used for the assessment of the effects of pomegranate juice on craving. It is consisted of 45 questions divided in 5 dimensions, namely desire to use heroin, intentions and planning to use heroin, anticipation of positive outcome, relief from withdrawal or dysphoria, and lack of control overuse. HCQ will be completed by the volunteers of both the experimental and control groups at four timepoints in order to assess the change on craving as follows: Before the start of the experiment (i.e., day 1 or baseline), in the middle of the experiment (i.e., day 60), at the end of the experiment (i.e., day 120), and 6 months after the end of the experiment (i.e., follow-up measurement).
Secondary Outcomes
- Determination of antioxidant enzyme Catalase (CAT)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the total antioxidant capacity (TAC) of plasma(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the capacity of plasma to reduce superoxide radical (O2•-)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the reducing power(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of interleukin-1 betta (IL-1b)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of interleukin-8 (IL-8)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- In vitro evaluation of antioxidant and reducing properties of the administered pomegranate juice(Day 1)
- Measurement of the capacity of plasma to reduce hydroxyl radical (OH•)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of GSH concentration(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the activity of the antioxidant enzyme glutathione peroxidase (GPx)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of protein carbonyls(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the activity of the antioxidant enzyme glutathione reductase (GR)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of interferon gamma (IFN-γ)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of thiobarbituric acid reactive substances (TBARS)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the activity of the antioxidant enzyme superoxide dismutase (SOD)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of interferon alpha-2 (IFN-a2)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of interleukin-1 alpha (IL-1a)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Quality of Life (QoL)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of monocyte chemoattractant protein-1 (MCP-1)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of tumor necrosis factor alpha (TNF-a)(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of melatonin(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
- Measurement of the concentration of cortisol(Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement))
Investigators
Christonikos Leventelis
Toxicologist, MSc, PhD
Organization Against Drugs (ΟΚΑΝΑ)