PsychiatryNUTRIDOPENCT05861544
NUTRItion-driven Detoxification of OPioid Addicted patiEnts
A study testing Pomegranate juice in people with Psychiatry, run by Organization Against Drugs (ΟΚΑΝΑ) at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Psychiatry
- What is being tested?
- Pomegranate juice
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteGreece
- Study dates
- 23 Mar 2023to 23 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Over 20 years of age
- Long-term heroin or other opioid drug use
- Suffering from physical and mental dependence due to chronic opioid use
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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.
Read the 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.
- Conditions
- Psychiatry
- Being tested
- Pomegranate juice
- Keywords
- Craving, Buprenorphine, Opioid use disorders, Methadone, Pomegranate juice, Redox biomarkers, Inflammation, Antioxidants, Nutrition
- Medical subject headings
- Opioid-Related Disorders, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pomegranate juiceDietary supplement
The pomegranate juice that will be used in the experiment is a 100% natural product without conservatives. It will kindly be donated from the company Rodi Hellas SA, Pella, Greece. The product is in line with the quality assurance certificates by the International Organization for Standardization (ISO 22000:2005), Global Gap, Grasp and Kosher.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | 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. Receives: Dietary Supplement: Pomegranate juice |
| Control group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Craving
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).
Measured: 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.
Secondary outcomes (22)
Quality of Life (QoL)
The Nottingham Health Profile (NHP) questionnaire will be used for the assessment of the pomegranate juice effects on the QoL of the patients. The questionnaire consists of two parts; the first part assesses parameters such as activity, pain, emotional reaction, sleep, social isolation, and mobility, whereas the second part evaluates the effects of health or disease on the activities of daily living.
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Determination of antioxidant enzyme Catalase (CAT)
Spectrophotometric evaluation of the activity of the antioxidant enzyme CAT expressed in U/gr Hb (haemoglobin) in red blood cell lysate (RBCL). The enzyme activity will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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
TAC will be evaluated spectrophotometrically in plasma expressed as mmol DPPH•/ml. TAC levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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
The antioxidant and reducing properties of pomegranate juice will be evaluated using specific in vitro tests: 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), hydroxyl radical, superoxide radical, Fe+3 to Fe2+ reduction) expressed in half maximal inhibitory concentration (IC50) (μl).
Measured: Day 1
Measurement of the concentration of protein carbonyls
Protein carbonyls, as a biomarker of protein oxidation, will be evaluated in plasma spectrophotometrically expressed in nmol/mg protein. The levels of protein carbonyls will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
TBARS, a biomarker of lipid peroxidation, will be evaluated in plasma spectrophotometrically expressed in μmol/l. The levels of TBARS will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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 hydroxyl radical (OH•)
Spectrophotometric evaluation of the ability of plasma to reduce hydroxyl radical expressed in mmol deoxyribose/ml. The reducing capacity of plasma will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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•-)
Spectrophotometric evaluation of the ability of plasma to reduce superoxide radical expressed in % scavenging capacity. The reducing capacity of plasma will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the reducing power
Spectrophotometric evaluation of the ability of plasma to reduce Fe+3 to Fe+2 expressed in mmol potassium ferricyanide/ml. The reducing capacity of plasma will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of GSH concentration
The reduced form of glutathione (GSH) as a crucial antioxidant molecule will be measured spectrophotometrically and its levels will be expressed in μmol/g Hb. GSH levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
The activity of the antioxidant enzyme SOD expressed in U/gr Hb (haemoglobin) will be measured in red blood cell lysate (RBCL). SOD activity levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
The activity of the antioxidant enzyme GPx expressed in U/gr Hb (haemoglobin) will be measured in red blood cell lysate (RBCL). GPx activity levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
The activity of the antioxidant enzyme GR expressed in U/gr Hb (haemoglobin) will be measured in red blood cell lysate (RBCL). GR activity levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
IFN-γ, expressed in pg/ml, is a cytokine that recruits macrophages at the site of inflammation. Its concentration will be assessed through immunofluorescence. IFN-γ levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
IFN-a2, expressed in pg/ml, regulates the activation of the immune system and inhibits cell proliferation. Its concentration will be assessed through immunofluorescence. IFN-a2 levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
IL-1b, expressed in pg/ml, is activated by macrophages and neutrophils and regulate immune response. Its concentration will be assessed through immunofluorescence. IL-1b levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
Chemokine IL-8, expressed in pg/ml, induces chemotaxis of neutrophils and other granulocytes in an inflammation site. Its concentration will be assessed through immunofluorescence. IL-8 levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
MCP-1,expressed in pg/ml, recruits monocytes, lymphocytes, and neutrophils at the site of inflammation. Its concentration will be assessed through immunofluorescence. MCP-1 levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
IL-1a, expressed in pg/m, regulates immune response after its activation by macrophages and neutrophils. Its concentration will be assessed through immunofluorescence. IL-1a levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: 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)
TNF-a, expressed in pg/ml, is realised by macrophages for cell signaling as part of the immune response. Its concentration will be assessed through immunofluorescence. TNF-a levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the concentration of melatonin
Melatonin is involved in circadian regulation through sleep-wake timing. Saliva samples will be taken at 22.00 in dim light by patients themselves under oral and typed guidelines. Dim light melatonin onset (DLMO) concentration will be measured using enzyme-linked immunosorbent assay (ELISA) and will be expressed in pg/ml. Melatonin levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the concentration of cortisol
Cortisol belongs to glycocorticoid class of hormones related with stress system and can weaken the activity of immune system through the releasing of cytokines in inflammation site. Plasma samples will be collected early in the morning and cortisol concentration will be expressed in pg/ml and be measured using enzyme-linked immunosorbent assay (ELISA). Cortisol levels will be compared between Day 1 (baseline) and the following time points: Day 60, Day 120, six months following the end of the experiment (follow-up measurement).
Measured: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2023
- Study start23 Mar 2023
- Primary completion23 Jul 2023 (estimated)
- Study completion23 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for PsychiatryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Organization Against Drugs (ΟΚΑΝΑ)
- Sponsor type
- Other government
- Collaborators
- University of Thessaly
- Responsible party
- Principal investigator, Christonikos Leventelis, Organization Against Drugs (ΟΚΑΝΑ)
- Investigators
- Christonikos Leventelis, Dr, Principal investigator, Organization against Drugs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05861544
- Sponsor's protocol ID
- 44482-2/12/2020
- Acronym
- NUTRIDOPE
- Status last verified
- May 2023
- First submitted
- 13 Apr 2023
- Last updated
- 17 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data obtained through this investigation will be provided to qualified researchers with related academic interest.
Publications
Abu-Taweel GM, Al-Mutary MG. Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice. J Trace Elem Med Biol. 2021 Dec;68:126842. doi: 10.1016/j.jtemb.2021.126842. Epub 2021 Aug 17.
PubMed 34418746Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem. 2006 Feb 8;54(3):980-5. doi: 10.1021/jf052005r.
PubMed 16448212Adel-Mehraban MS, Tansaz M, Mohammadi M, Yavari M. Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial. Complement Ther Clin Pract. 2022 Feb;46:101544. doi: 10.1016/j.ctcp.2022.101544. Epub 2022 Feb 2.
PubMed 35134697Ahmadi J, Jahromi MS, Ghahremani D, London ED. Single high-dose buprenorphine for opioid craving during withdrawal. Trials. 2018 Dec 10;19(1):675. doi: 10.1186/s13063-018-3055-z.
PubMed 30526648Aliyu IM, Danladi S, Ibrahim UI, Al-kassim Hassan M, Rohin MAK and Mohamad N (2018) Therapeutic potential of pomegranate antioxidant compounds in ameliorating opiate addiction. The Pharma Innovation Journal 7(5): 668-672.
Brown R, Kraus C, Fleming M, Reddy S. Methadone: applied pharmacology and use as adjunctive treatment in chronic pain. Postgrad Med J. 2004 Nov;80(949):654-9. doi: 10.1136/pgmj.2004.022988.
PubMed 15537850Browne CJ, Godino A, Salery M, Nestler EJ. Epigenetic Mechanisms of Opioid Addiction. Biol Psychiatry. 2020 Jan 1;87(1):22-33. doi: 10.1016/j.biopsych.2019.06.027. Epub 2019 Jul 8.
PubMed 31477236Cambay Z, Baydas G, Tuzcu M, Bal R. Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats. Acta Physiol Hung. 2011 Dec;98(4):409-20. doi: 10.1556/APhysiol.98.2011.4.4.
PubMed 22173022Chen SL, Lee SY, Tao PL, Chang YH, Chen SH, Chu CH, Chen PS, Lee IH, Yeh TL, Yang YK, Hong JS, Lu RB. Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment. J Neuroimmune Pharmacol. 2012 Dec;7(4):1025-33. doi: 10.1007/s11481-012-9400-1. Epub 2012 Sep 19.
PubMed 22990619Dunn KE, Finan PH, Andrew Tompkins D, Strain EC. Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients. Addict Behav. 2018 Jan;76:8-14. doi: 10.1016/j.addbeh.2017.07.016. Epub 2017 Jul 14.
PubMed 28735039Estrada-Camarena EM, Lopez-Rubalcava C, Ramirez-Rodriguez GB, Pulido D, Cervantes-Anaya N, Azpilcueta-Morales G, Granados-Juarez A, Vega-Rivera NM, Islas-Preciado D, Trevino S, de Gortari P, Gonzalez-Trujano ME, Garcia-Viguera C. Aqueous extract of pomegranate enriched in ellagitannins prevents anxiety-like behavior and metabolic changes induced by cafeteria diet in an animal model of menopause. Neurochem Int. 2020 Dec;141:104876. doi: 10.1016/j.neuint.2020.104876. Epub 2020 Oct 10.
PubMed 33049337Fahmy HA, Farag MA. Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical. J Food Biochem. 2022 Jan;46(1):e14024. doi: 10.1111/jfbc.14024. Epub 2021 Dec 19.
PubMed 34923641Garratt M, Brooks RC. A genetic reduction in antioxidant function causes elevated aggression in mice. J Exp Biol. 2015 Jan 15;218(Pt 2):223-7. doi: 10.1242/jeb.112011. Epub 2014 Dec 18.
PubMed 25524980Guerrero-Solano JA, Jaramillo-Morales OA, Velazquez-Gonzalez C, De la O-Arciniega M, Castaneda-Ovando A, Betanzos-Cabrera G, Bautista M. Pomegranate as a Potential Alternative of Pain Management: A Review. Plants (Basel). 2020 Mar 30;9(4):419. doi: 10.3390/plants9040419.
PubMed 32235455Hajipour S, Sarkaki A, Mohammad S, Mansouri T, Pilevarian A, RafieiRad M. Motor and cognitive deficits due to permanent cerebral hypoperfusion/ischemia improve by pomegranate seed extract in rats. Pak J Biol Sci. 2014 Aug;17(8):991-8. doi: 10.3923/pjbs.2014.991.998.
PubMed 26031017
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05861544
- Acronym / sponsor ID
- NUTRIDOPE / 44482-2/12/2020
- Conditions
- Psychiatry
- Keywords
- Craving, Buprenorphine, Opioid use disorders, Methadone, Pomegranate juice, Redox biomarkers, Inflammation, Antioxidants
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Organization Against Drugs (ΟΚΑΝΑ)Other government
- Collaborators
- University of Thessaly
- Study start
- 23 Mar 2023 (actual)
- Primary completion
- 23 Jul 2023 (estimated)
- Study completion
- 23 Jan 2024 (estimated)
- First posted
- 17 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Dietary Supplement: Pomegranate juicePatients 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. |
| Control group | No intervention | –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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Over 20 years of age
- Long-term heroin or other opioid drug use
- Suffering from physical and mental dependence due to chronic opioid use
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pomegranate juiceThe pomegranate juice that will be used in the experiment is a 100% natural product without conservatives. It will kindly be donated from the company Rodi Hellas SA, Pella, Greece. The product is in line with the quality assurance certificates by the International Organization for Standardization (ISO 22000:2005), Global Gap, Grasp and Kosher. | Dietary supplement | Experimental group |
Primary outcome
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).
22 secondary outcomes
Quality of Life (QoL)
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Determination of antioxidant enzyme Catalase (CAT)
Time frame: 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
Time frame: 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
Time frame: Day 1
Measurement of the concentration of protein carbonyls
Time frame: 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)
Time frame: 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 hydroxyl radical (OH•)
Time frame: 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•-)
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the reducing power
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of GSH concentration
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the concentration of melatonin
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Measurement of the concentration of cortisol
Time frame: Day 1; Day 60; Day 120, six months following the end of the experiment (follow-up measurement)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2023.
- Background: PubMed 34418746Abu-Taweel GM, Al-Mutary MG. Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice. J Trace Elem Med Biol. 2021 Dec;68:126842. doi: 10.1016/j.jtemb.2021.126842. Epub 2021 Aug 17.
- Background: PubMed 16448212Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem. 2006 Feb 8;54(3):980-5. doi: 10.1021/jf052005r.
- Background: PubMed 35134697Adel-Mehraban MS, Tansaz M, Mohammadi M, Yavari M. Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial. Complement Ther Clin Pract. 2022 Feb;46:101544. doi: 10.1016/j.ctcp.2022.101544. Epub 2022 Feb 2.
- Background: PubMed 30526648Ahmadi J, Jahromi MS, Ghahremani D, London ED. Single high-dose buprenorphine for opioid craving during withdrawal. Trials. 2018 Dec 10;19(1):675. doi: 10.1186/s13063-018-3055-z.
- BackgroundAliyu IM, Danladi S, Ibrahim UI, Al-kassim Hassan M, Rohin MAK and Mohamad N (2018) Therapeutic potential of pomegranate antioxidant compounds in ameliorating opiate addiction. The Pharma Innovation Journal 7(5): 668-672.
- Background: PubMed 15537850Brown R, Kraus C, Fleming M, Reddy S. Methadone: applied pharmacology and use as adjunctive treatment in chronic pain. Postgrad Med J. 2004 Nov;80(949):654-9. doi: 10.1136/pgmj.2004.022988.
- Background: PubMed 31477236Browne CJ, Godino A, Salery M, Nestler EJ. Epigenetic Mechanisms of Opioid Addiction. Biol Psychiatry. 2020 Jan 1;87(1):22-33. doi: 10.1016/j.biopsych.2019.06.027. Epub 2019 Jul 8.
- Background: PubMed 22173022Cambay Z, Baydas G, Tuzcu M, Bal R. Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats. Acta Physiol Hung. 2011 Dec;98(4):409-20. doi: 10.1556/APhysiol.98.2011.4.4.
- Background: PubMed 22990619Chen SL, Lee SY, Tao PL, Chang YH, Chen SH, Chu CH, Chen PS, Lee IH, Yeh TL, Yang YK, Hong JS, Lu RB. Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment. J Neuroimmune Pharmacol. 2012 Dec;7(4):1025-33. doi: 10.1007/s11481-012-9400-1. Epub 2012 Sep 19.
- Background: PubMed 28735039Dunn KE, Finan PH, Andrew Tompkins D, Strain EC. Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients. Addict Behav. 2018 Jan;76:8-14. doi: 10.1016/j.addbeh.2017.07.016. Epub 2017 Jul 14.
- Background: PubMed 33049337Estrada-Camarena EM, Lopez-Rubalcava C, Ramirez-Rodriguez GB, Pulido D, Cervantes-Anaya N, Azpilcueta-Morales G, Granados-Juarez A, Vega-Rivera NM, Islas-Preciado D, Trevino S, de Gortari P, Gonzalez-Trujano ME, Garcia-Viguera C. Aqueous extract of pomegranate enriched in ellagitannins prevents anxiety-like behavior and metabolic changes induced by cafeteria diet in an animal model of menopause. Neurochem Int. 2020 Dec;141:104876. doi: 10.1016/j.neuint.2020.104876. Epub 2020 Oct 10.
- Background: PubMed 34923641Fahmy HA, Farag MA. Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical. J Food Biochem. 2022 Jan;46(1):e14024. doi: 10.1111/jfbc.14024. Epub 2021 Dec 19.
- Individual participant dataSharing planned: Yes. Data obtained through this investigation will be provided to qualified researchers with related academic interest.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christonikos Leventelis, Dr principal investigator
Organization against Drugs
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pomegranate juice in people with Psychiatry, run by Organization Against Drugs (ΟΚΑΝΑ) at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05861544, which also lists 33 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2023.