Moringa Oleifera- Antiretroviral Pharmacokinetic Drug Interaction

Study Overview
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Brief Summary
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A study will be conducted by scientists from the University of Zimbabwe to determine if antiretroviral drugs are affected by taking herbs at the same time. This is important because herbal medicines may interact with modern medicine to increase or decrease the amount of medication in the body. The drugs nevirapine and efavirenz will be studied. Both drugs are routinely used as part of combination therapy for treating HIV. In this study it will be determined whether the concentrations of the antiretroviral drugs nevirapine and efavirenz are low, high or are in the desired range when taken together with the herb moringa.

Detailed Description
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The use of herbal supplements is widespread in Africa, particularly for the management of HIV and AIDS. In Zimbabwe, the prevalence of herbal medicine use in HIV-infected people is as high as 79% (Sebit et al., 2000). Several studies have shown that the herb Moringa oleifera is among the top 10 herbs most commonly used by HIV-positive people in Zimbabwe (Makomeya et al 2004, Monera et al 2008). Another review also cited Moringa as one of the 53 most important African medicinal plants presently traded (van den Bout-van den Beukel et al 2006). Others included Hypoxis hemerocallidea (African potato) and Sutherlandia frutescens-(Cancer bush). Moringa is rich in β-carotene, protein, vitamin C, calcium and potassium and act as a good source of natural antioxidants (Anwar et al.,2007).It is recommended by non-governmental organisations and some African governments as an immune booster and a nutritional supplement for people living with HIV and AIDS (Ncube, 2006). Most advocates and users believe that since the herb is natural, it is free from all side effects and interactions. Concomitant use of herbs with conventional drugs may lead to herb-drug interactions in the same way that two or more co-administered drugs may interact. Herbal constituents that are substrates for the same enzymes or transporters of conventional drugs may induce or inhibit the enzymes and/or transporter activity. Pharmacokinetic endpoints such as area under the curve (AUC), time to maximum plasma concentration (tmax), peak plasma concentration (Cmax), trough concentration (Cmin), clearance (CL), volume of distribution (Vd/F) and half-life (T1/2) may be altered significantly resulting in toxicity, more severe adverse effects, sub-therapeutic drug concentrations, HIV resistance and treatment failure.The risk of interaction increases as the number of co-administered drugs increases (de Maat et al 2003). As a result, people taking herbal medicines while on antiretroviral therapy are at very high risk because of the multitude use of highly active antiretroviral drugs and treatment of opportunistic infections, and also because herbs contain a wide range of bioactive chemical constituents. However, evidence based information of such effects is usually lacking and as such; health practitioners' ability to make relevant clinical decisions is limited. Results of a review of in vitro studies suggest a need for in vivo metabolic drug-drug interaction studies (van den Bout-van den Beukel et al 2006). Preliminary in vivo studies in animal models can serve as a basis for clinical trials, the results of which are considered the gold standard in this era of evidence-based medicine. Primary objectives To compare the steady-state pharmacokinetics of nevirapine and efavirenz in HIV-positive patients before and after supplementation with Moringa oleifera leaf powder To compare the single dose pharmacokinetics of nevirapine and efavirenz in rat models before and after supplementation with Moringa oleifera leaf powder Secondary objectives To determine the bioavailability of Moringa oleifera leaf powder in humans after oral dosing using beta carotene as a bio marker. To compare urine chemistries and liver function tests in HIV patients before and after supplementation with Moringa oleifera leaf powder To determine the presence of any genetic variation in the participants in the genes that code for CYP3A4 and CYP2B6

Official Title
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Effect of Moringa Oleifera (Moringa, Drumstick/Horseradish Tree) on The Pharmacokinetics of Efavirenz and Nevirapine In-vivo.

Conditions
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HIV

Intervention / Treatment
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* Dietary Supplement: Moringa oleifera
* Drug: Efavirenz 600mg
* Drug: Nevirapine 200Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positive, ≥ 4 weeks on Nevirapine or , ≥ 2 weeks on Efavirenz containing regimen, Supplements HAART with Moringa oleifera. Exclusion Criteria: Known hepatic, intestinal or renal disease,smoking, chronic alcohol ingestion, poor venous access, chronic alcohol ingestion, pregnant, smoking, on rifampicin, ketoconazole, isoniazid, breastfeeding, anaemia,vomiting

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Nevirapine<br>HIV positive patients on nevirapine containing regimen, taking Moringa oleifera leaf powder | Dietary Supplement: Moringa oleifera<br>* leaf powder, 1.85g once daily, hard gelatin capsules<br>* Other names: horseradish tree;Drug: Nevirapine 200Mg Oral Tablet<br>* Nevirapine 200mg based regimen<br>|
| Efavirenz<br>HIV positive patients on efavirenz containing regimen, taking Moringa oleifera | Dietary Supplement: Moringa oleifera<br>* leaf powder, 1.85g once daily, hard gelatin capsules<br>* Other names: horseradish tree;Drug: Efavirenz 600mg<br>* Efavirenz 600mg based regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the plasma concentration time curve, determined using a non-compartmental approach by means of the Phoenix WinNonlin software application. Time points for sample collection were 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h | Baseline (day 22), Post-moringa (day 35) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C12h | plasma concentration 12h post dose, determined using a non-compartmental approach by means of the Phoenix WinNonlin software application. Time points for sample collection were 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h | Baseline (Day 22); Post-moringa (Day 35) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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herbal medicine, HIV, antiretroviral drug interaction, pharmacokinetics, herbal pharmacology