Design and Objectives of the ELCIE Clinical Trial

June 13, 2019

Effects of rhLactoferrin on Chronic Inflammation in the Elderly: Design and Objectives of the ELCIE Clinical Trial

We have previously introduced an ongoing clinical study, headed by principal investigator Jeremy Walston, MD,  Johns Hopkins School of Medicine, aimed at finding out if recombinant human lactoferrin (rhLactoferrin) produced from Ventria Bioscience’s ExpressTec biologic manufacturing system may improve mobility and memory versus placebo in adults with chronic inflammation.

Chronic Inflammation Affects Cognition and Physical Mobility

The scientific impetus behind this study represents the synthesis of a number of important prior clinical findings. First, chronic inflammation is known to negatively affect both physiological functional status and cognitive performance, and this effect is exacerbated with increasing age. Thus, chronic inflammation and associated increases in levels of the cytokines interleukin-6 (IL-6) and tumor necrosis factor receptor 1 (TNFR1) have been correlated with functional disability, lower muscle mass, strength, and frailty in elderly people or people with chronic stress.1–4 Furthermore, chronic inflammation is also strongly correlated with cognitive decline, depression, and dementia in the elderly.5–9 Of particular interest, increasing frailty with loss of iron hemostasis in the brain causes oxidative stress, increasing levels of non-heme iron in the brain tissues, and chronic inflammation—all associated with brain aging and poor cognition.3

Another key scientific finding is that that the protein lactoferrin may confer a therapeutic benefit in reducing the downstream effects of chronic inflammation and inflammatory bowel disease . Lactoferrin, a member of the transferrin protein family, is a key component of human breastmilk and other human secretory fluids, as well as blood plasma. It is essential for immune health, gut health, and for regulation of cellular iron transport and iron hemostasis.

The ELCIE Clinical Study: Design and Objectives

With this evidence as the background, Ventria Bioscience is engaged in an active collaboration with researchers at Johns Hopkins University to carry out a a phase 2, randomized, controlled clinical trial, Effects of rhLactoferrin on Chronic Inflammation in the Elderly (ELCIE).

The purpose of this study, which completed enrollment in February, is to “investigate how recombinant human lactoferrin which is a partially iron saturated form of lactoferrin produced by ExpressTec improves mobility and memory in older adults with chronic inflammation.”

ELCIE is a randomized, two-arm, parallel-assignment, double-blinded clinical study in 36 participants age 70 years or older. Participants must show evidence of impaired mobility (walking speed <1.0 m/sec by 4-meter timed walk) and elevated biomarkers of inflammation (serum IL-6 level ≥ 2.5 pg/ml or TNFR1 level ≥1500 pg/ml) at baseline but not be taking daily anti-inflammatory drugs or have mobility disabilities due to Parkinson’s disease, stroke, or symptomatic cardiovascular disease.

Once randomized, participants will receive 1500 mg of recombinant human lactoferrin (experimental arm) or a matching placebo (control arm) in capsule form, twice daily for six months. Throughout the study, participants will be evaluated for levels of inflammatory biomarkers in their blood serum as well as changes in measures of physical and cognitive ability.

The primary outcome measures will be the effect of rhLactoferrin on serum levels of IL-6 and TNFR1 over 6 months of treatment. Secondary outcome measures include attenuation of cognitive decline by the digital symbol substitution test and two trail-making tests; physical mobility by 4-meter walk and 6-minute walk tests; tolerability; and medication adherence.

In the end, the investigators hope to determine if rhLactoferrin has the potential to safely improve measures of chronic inflammation in older adults, along with associated measures of physical and cognitive function. The results of this trial will inform future development of recombinant human lactoferrin for therapeutic use.

References:

  1. Valdiglesias V, Sánchez-Flores M, Maseda A et al. Immune biomarkers in older adults: Role of physical activity. J Toxicol Environ Health A. 2017;80(13-15):605-620. https://doi.org/10.1080/15287394.2017.1286898
  2. Tay L, Lim WS, Chan M, Ye RJ, Chong MS. The Independent Role of Inflammation in Physical Frailty among Older Adults with Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease. J Nutr Health Aging. 2016;20(3):288-299. https://doi.org/10.1007/s12603-015-0617-6
  3. Daugherty AM, Raz N. Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods. Neuropsychol Rev. 2015;25(3):272-287. https://doi.org/10.1007/s11065-015-9292-y
  4. Thomas DR. The relationship between functional status and inflammatory disease in older adults. J Gerontol A Biol Sci Med Sci. 2003;58(11):995-998. https://doi.org/10.1093/gerona/58.11.m995
  5. Beydoun MA, Dore GA, Canas JA et al. Systemic Inflammation Is Associated With Longitudinal Changes in Cognitive Performance Among Urban Adults. Front Aging Neurosci. 2018;10:313. https://doi.org/10.3389/fnagi.2018.00313
  6. Sala-Llonch R, Idland AV, Borza T et al. Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition. J Alzheimers Dis. 2017;58(3):829-840. https://doi.org/10.3233/JAD-161146
  7. Sartori AC, Vance DE, Slater LZ, Crowe M. The impact of inflammation on cognitive function in older adults: implications for healthcare practice and research. J Neurosci Nurs. 2012;44(4):206-217. https://doi.org/10.1097/JNN.0b013e3182527690
  8. Trollor JN, Smith E, Agars E et al. The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study. Age (Dordr). 2012;34(5):1295-1308. https://doi.org/10.1007/s11357-011-9301-x
  9. Simen AA, Bordner KA, Martin MP, Moy LA, Barry LC. Cognitive dysfunction with aging and the role of inflammation. Ther Adv Chronic Dis. 2011;2(3):175-195. https://doi.org/10.1177/2040622311399145