Moringa Oleifera- Antiretroviral Pharmacokinetic Drug Interaction

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01410058
• Other study ID #: MO 001
• Status: Completed
• Start date: January 2013
• Est. completion date: September 2013

Study information

• Verified date: March 2019
• Source: University of Zimbabwe
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV

Intervention

Dietary Supplement:
• Moringa oleifera
leaf powder, 1.85g once daily, hard gelatin capsules

Drug:
• Efavirenz 600mg
Efavirenz 600mg based regimen
• Nevirapine 200Mg Oral Tablet
Nevirapine 200mg based regimen

Locations

Country	Name	City	State
Zimbabwe	Parirenyatwa Hospital OI Clinic	Harare

Sponsors (3)

Lead Sponsor	Collaborator
University of Zimbabwe	Biomedical Research and Training Institute, State University of New York at Buffalo

Country where clinical trial is conducted

Zimbabwe, 

References & Publications (3)

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. Review. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cmax	Maximum plasma concentration post does, 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)
Primary	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	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)