This paper describes the protocols of two randomized controlled clinical trials within the TENLEP study. In the Clinical trial the effect of long term prednisolone treatment on the restoration of clinical NFI will be investigated. In the Subclinical trial the efficacy of prednisolone in preventing the development of clinical NFI, in patients with subclinical neuropathy, will be examined.
The optimal dose and duration of prednisolone for treating clinical NFI in leprosy has not been established yet and there is not enough evidence available from randomized controlled clinical trials on the long term effect of prednisolone treatment [3
]. The TENLEP study addresses this knowledge gap and will extend the current understanding of prednisolone regimens for the treatment of clinical NFI by comparing a prednisolone treatment of 32 weeks and 20 weeks under controlled circumstances. If a 32 weeks treatment proves to be effective in restoring or improving clinical NFI in leprosy patients, new guidelines can be developed which can significantly improve patient management in leprosy care and especially a positive effect on the prevention of disabilities (POD) can be expected.
This study will be the first to evaluate prednisolone treatment for the prevention of clinical NFI in people affected by leprosy diagnosed with subclinical neuropathy. The results of the preceding TRIPOD trial provide some insight in possible effects of prednisolone in preventing new NFI [28
]. To prevent new NFI and reactions, leprosy patients with and without pre-existing NFI at diagnosis (as determined with VMT and MFT) received a prophylactic low dose of prednisolone (20 mg/day) for four months, tapered down in the last month. Although a reduced incidence of new NFI and reactions was observed at the end of treatment at four months, this was not sustained at one year. More important however, the preventive effect of prednisolone at four months was more than three times higher in patients with no pre-existing NFI [28
]. A second study that has some similarities with our Subclinical trial is of that of Capadia et al. [29
], who studied the effect of prednisolone on neuropathy as assessed with NCS. In their study, neuropathy was divided in mild, moderate and severe groups, as percentages deviating from normative values. Their findings suggest that a 12-week prednisolone course is not effective in preventing or reversing nerve damage. However, they found that mildly affected nerves showed higher improvement rates than moderately and severely affected nerves (53%, 21% and 14% of the nerves improved respectively).
The better outcomes of prednisolone treatment and prophylaxis on non-affected and mildly affected nerves from both studies of TRIPOD and Capadia et al. [29
] show the importance of early treatment of neuropathy in leprosy patients. With the Subclinical trial we hope to establish that prednisolone treatment can prevent the development of clinical NFI and in this way can prevent disabilities and deformities in newly diagnosed leprosy patients.
If the prednisolone treatment turns out to be effective in the prevention of clinical NFI, the implementation of treatment for patients with evident subclinical neuropathy in clinical practice will be complicated. The methods to detect subclinical neuropathy used in this study (TSA II and Neurocare 2000) will not be available in the field, since the devices are expensive and conditions under which the assessments have to take place, a steady environmental temperature of 20–25°C, are difficult to realize in tropical climates. Therefore it is important to search for a cheaper, portable method to detect subclinical neuropathy that can be easily used in field clinics.
However, also without a test to determine subclinical neuropathy the results of this study can be useful to improve treatment guidelines. The current prediction rule allows to distinguish leprosy patients with a high risk for developing NFI [30
]. However, at the moment, providing prophylactic prednisolone treatment to this group of patients is considered unethical, as a significant number of patients will take prednisolone unnecessarily. With the information of the TENLEP trials we hope the prediction rule can be refined, so administering prophylactic prednisolone is acceptable in certain, well defined groups.
In conclusion, the TENLEP study will add to the current understanding of neuropathy due to leprosy and will provide better insight into the effectiveness of prednisolone treatment in the prevention and recovery of nerve function loss in leprosy patients. If this study shows the effectiveness of prednisolone in the prevention and recovery of NFI it will improve treatment options and contribute therefore to the prevention of permanent sensory and/or motor nerve function loss in people affected by leprosy and hence prevent disabilities and deformities which will improve the lives of many of these patients.