Clinical trial NCT01410058: Moringa Oleifera- Antiretroviral Pharmacokinetic Drug Interaction
Official title: Effect of Moringa Oleifera (Moringa, Drumstick/Horseradish Tree) on The Pharmacokinetics of Efavirenz and Nevirapine In-vivo.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Keywords: HIV
antiretroviral drug interaction
herbal medicine
pharmacokinetics
herbal pharmacology
Lead sponsor: University of Zimbabwe
Sponsor class: OTHER
Collaborators: name: State University of New York at Buffalo
name: Biomedical Research and Training Institute
First posted: 2011-08-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: HIV Opportunistic infections clinic

Brief summary: 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: 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

1. To compare the steady-state pharmacokinetics of nevirapine and efavirenz in HIV-positive patients before and after supplementation with Moringa oleifera leaf powder
2. To compare the single dose pharmacokinetics of nevirapine and efavirenz in rat models before and after supplementation with Moringa oleifera leaf powder

   Secondary objectives
3. To determine the bioavailability of Moringa oleifera leaf powder in humans after oral dosing using beta carotene as a bio marker.
4. To compare urine chemistries and liver function tests in HIV patients before and after supplementation with Moringa oleifera leaf powder
5. To determine the presence of any genetic variation in the participants in the genes that code for CYP3A4 and CYP2B6

Eligibility criteria: 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

Primary outcomes:
measure: AUC
timeFrame: Baseline (day 22), Post-moringa (day 35)
Secondary outcomes:
measure: C12h
timeFrame: Baseline (Day 22); Post-moringa (Day 35)
Other outcomes:
measure: Cmax
timeFrame: Baseline (day 22), Post-moringa (day 35)
Locations:
city: Harare
country: Zimbabwe
facility: Parirenyatwa Hospital OI Clinic
Study officials:
affiliation: University of Zimbabwe
name: Tsitsi G Monera, BPharmHons, MPhil, MSc CT
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res. 2007 Jan;21(1):17-25. doi: 10.1002/ptr.2023.
citation: Sebit MB, Chandiwana SK, Latif AS, Gomo E, Acuda SW, Makoni F, Vushe J. Quality of life evaluation in patients with HIV-I infection: the impact of traditional medicine in Zimbabwe. Cent Afr J Med. 2000 Aug;46(8):208-13.
citation: van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burger DM. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metab Rev. 2006;38(3):477-514. doi: 10.1080/03602530600754065.
citation: Monera-Penduka TG, Maponga CC, Wolfe AR, Wiesner L, Morse GD, Nhachi CF. Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study. AIDS Res Ther. 2017 Mar 14;14:12. doi: 10.1186/s12981-017-0140-4. eCollection 2017.
citation: Monera-Penduka TG, Maponga CC, Morse GD, Nhachi CFB. Capacity for ethical and regulatory review of herbal trials in developing countries: a case study of Moringa oleifera research in HIV-infected patients. J Pharm Policy Pract. 2017 Feb 20;10:9. doi: 10.1186/s40545-017-0099-5. eCollection 2017.