Natural clinical trials

Natural Products Clinical Trials Resource. NCCIH supports clinical research that uses natural products, including botanicals, dietary supplements, vitamins, minerals, and probiotics. The U. Food and Drug Administration FDA establishes and enforces the regulatory requirements for clinical research on natural products when they may be used as drugs.

Only the FDA has the authority to interpret and enforce its regulatory requirements and to make decisions about whether proposed clinical research needs an Investigational New Drug IND application.

Study record managers: refer to the Data Element Definitions if submitting registration or results information. This study investigates an innovative treatment for relapsed or refractory acute myeloid leukemia AML exploiting administration of ex vivo-generated allogeneic natural killer NK cells with preceding non-myeloablative conditioning chemotherapy with or without subsequent in vivo IL-2 cytokine support. The first phase is a IL-2 dose-escalating safety study in twelve patients.

The second phase of the study is designed as a Simon's optimal two-stage single-arm phase IIa study, comprising seventeen patients. On day 0, all patients will receive a fixed dose of 1. After establishing the safety of UCB-NK cells combined with SC IL-2, we will continue with phase IIa of the study, with ten patients in the first stage including the six patients from phase I with comparable IL-2 dose and if clinical efficacy is achieved an additional seven patients in the second stage.

Three patients will receive NK cells without IL If no dose limiting toxicities occur another three patients will receiving NK cells with a low dose IL-2, and if safe, another six patients will receive NK cells with a higher dose IL Therefore 17 patients will be evaluated using a Simon's optimal two-stage single-arm study design, with 10 patients in the first stage and an additional 7 patients in the second stage. These patients will receive NK cells with the highest tolerable dose IL-2, established after phase I.

NK cells administration will not be followed by sc IL IL-2 will be administered in a fixed dose of 3. IL-2 will be administered in a fixed dose of 6. If in any of the three patients of each individual cohort of the phase I study a DLT occurs, the cohort will be extended to 6 patients.

If 2 patients experience DLT within a cohort of 3 or 6 patients the study will be stopped in case the patients were only receiving NK cells or the study will be continued without IL-2 or the lower dose of IL-2 in case the patients were receiving NK cells in combination with IL Serious, life threatening adverse events or grade 4 toxicity will be a reason to terminate the study or continue without IL-2 cytokine support.

Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Patients may belong to any of the following categories:. Try the modernized ClinicalTrials.

Learn more about the modernization effort. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. The following types of clinical trials are not intended to be supported by this FOA and applications proposing such clinical trials will not be considered for funding :. Early contact 12 weeks prior to submission is encouraged provides an opportunity for IC staff to discuss the scope and goals, and to provide information and guidance.

Other Information for award authorities and regulations. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. Need help determining whether you are doing a clinical trial?

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the requested project award period. The period of award for the UH3 phase is expected to be 4 years. With strong justification, up to 6 years for the UH3 may be requested. Non-domestic non-U.

Entities Foreign Institutions are not eligible to apply. Organizations are not eligible to apply. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible.

The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission. Obtaining an eRA Commons account can take up to 2 weeks. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:. See your administrative office for instructions if you plan to use an institutional system-to-system solution. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information:. Martina Schmidt, Ph. Titles may not exceed characters in length, including the tag, e. The Cover Letter is one pdf file only. Each site should submit an identical listing. If applicable, the letter should indicate the name of the NCCIH program officer with whom the project has been discussed.

Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations. Documentation of availability of eligible subjects at clinic sites, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the clinical study or trial.

Specifically, applicants must provide evidence that each recruiting center in the study or trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multi-site applications, information must be provided for each participating site. The following attachments must be included as a part of the cooperative agreement application.

Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed. The synopsis will provide a concise snapshot of the overall trial. It will be considered by reviewers, in addition to the components of the regular application. The synopsis is meant to supplement the information provided in the Research Strategy.

The Clinical Protocol Synopsis should represent the protocol that would be implemented at each site. It is meant to summarize the necessary elements of the clinical trial.

The Study Organization plan should describe the study organization and administration, and include a communication plan. The Study Organization plan can include, but is not necessarily limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any sub-contractors or providers of services, personnel, or facilities.

The plan should explain how these will integrate with the organizational framework described in the collaborating DCC application and should address how the CCC and DCC will coordinate leadership for clinical trial implementation. The communication plan should include a description of the coordination between the separate components including NCCIH and identify the key channels used to reach and inform each stakeholder group and receive feedback.

The Regulatory Communication plan should describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary to the conduct of the trial; and associated timeline. If the protocol is conducted under a non-US regulatory agency the applicant should submit a plan for attaining those regulatory approvals.

See additional requirements regarding IND submission in Section 6. If the proposed clinical trial does not include a device, natural product, or drug, this document should provide a brief statement as to why FDA regulation is not applicable. Applicants must provide a detailed table listing the characteristics of trials that demonstrate experience in trial coordination in the last 5 years.

The table must be provided as an attachment called " Clinical Trial Experience. The Project Management Plan should describe the evidence-based strategy that will be used throughout the project to ensure that the unique goals of the clinical trial are met.

Project management planning should directly support the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives.

The project management plan should describe the planning team and identify control points and processes that are key to scientific and fiscal performance. This will include a description of the organizational strategy that defines internal control points and business roles.

The management plan should also describe how the team, in collaboration with the DCC, will pro-actively evaluate and prioritize issues that jeopardize study goals and lead to the development of corrective responses to resolve fiscal and logistical issues risk planning in a timely manner.

Describe processes required for orderly project closure. In summary, the project management plan should provide sufficient detail to demonstrate the ability to achieve the goals of the clinical trial on-budget and on-time.

The project management plan should include risk mitigation or contingency plans. The plan should describe the key milestones that need to be met throughout the lifecycle of the clinical trial UG3 and UH3 phases to ensure its success; the processes that will be used to reach the milestones; and a timetable identifying when each of these key milestones will be met this can be provided as a table or a graph. All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity.

Milestones must be relevant, achievable, and measurable. The milestone plan should include anticipated challenges to meeting milestones and propose potential mitigation or corrective actions strategies. UH3 milestones should address overall recruitment and retention goals.

CCC milestones of particular interest during the UG3 phase that should be described in the application may include but are not limited to:. The application should also include a series of milestones for the completion of the specific aims of the clinical trial UH3 phase and contingency plans.

CCC milestones of particular interest during the UH3 phase that should be included in the application include but are not limited to:. Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. NCCIH staff will closely monitor progress at all trial stages including milestones, accrual, and safety.

The experience of all key personnel must be carefully documented. Most clinical trials will require a multidisciplinary team clinician, statistician, data manager, study coordinator s , etc. If parts of the costs of the trial are to be provided by sources other than NCCIH, these contributions must be presented in detail in the budget justification.

An independent DSMB will be established to monitor data and oversee participant safety in the clinical trial. The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application must present an overview of the state of the science, current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection, analysis, and dissemination. Significance : The significance of the proposed clinical trial and importance of the question must be clearly stated.

It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and why there is clinical equipoise. The application should make clear the need for and timeliness of the study with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area.

A discussion of the costs and benefits of the study should be included for evaluation of the trial's significance. Innovation : Explain how the application challenges and seeks to shift current research or clinical practice paradigms. Approach : The research approach section should include a description of the supporting data, clinical trial experience, the experimental approach, and a milestone plan. Supporting Data : The studies that led to the proposed clinical trial should be presented.

Data from pilot studies which show the need for and the feasibility of the trial should also be presented. Additional supporting data from other research should be included so that the approach chosen is clearly justified and adequately framed.

Applications must include the following preliminary data from human studies of the same product and specific formulation as proposed in the current application preferably published in the literature :. In these circumstances the applicant should: 1 provide a clear rationale and justification for why studying a biological signature in human participants is impossible or impractical; 2 consider proposing other objective, reproducible measures, that may be proxy to, or indicative of a biological or behavioral effect for the natural product; and 3 provide strong compelling preliminary data to warrant further study of a natural product in clinical studies.

Experimental Approach : The proposed experimental approach should include an appropriate design and the rationale for the particular design chosen e. The experimental approach description should include:. Subsequently, the DSMB will monitor and review recruitment, adverse events, data quality, outcome data, and overall awardee performance. The DSMB has the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early.

Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to the NCCIH. The DSMB will meet in person or by phone at least twice a year.

Applicants should not propose DSMB members in the application, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit. For revision applications, applicants should provide a list of the DSMB members in the application.

Letters of support from clinicians or clinical department chairs whose support is necessary to the successful conduct of the trial should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center. In addition, a letter of support should document that sufficient supply of the natural product will be available for testing at the time of award, including expiration date; the supplier will meet CMC specifications; and the supplier will provide the data necessary for the investigator to adhere to NIH and FDA policies.

Documentation should include a letter of agreement from the 3rd party supplying the natural product. If parts of the costs of the trial are to be provided by sources other than NCCIH, provide Letter s of Support signed by an authorized representative. Do not use the Appendix to circumvent page limits.

See Part 1. Section III. Part I.