TrialNavigator

I started this project the same way I start most of them: with a literature search to understand what already existed. The question was simple enough: is there an automated trial matching tool for CACNA1A patients?

Nope. There are OpenFDA API wrappers, commercial pharmacovigilance platforms, and general-purpose clinical trial aggregators aimed at researchers. The CACNA1A Foundation has a trials page, but it's manually maintained. There is no tool that continuously monitors ClinicalTrials.gov for CACNA1A-related studies, translates criteria, maps sites, and delivers updates to families via email.

The ClinicalTrials.gov API (REST v2) is free, requires no authentication, and returns well-structured JSON for up to 100 results per query. Running four queries (across CACNA1A, familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6) and deduplicating on NCT ID gives a comprehensive view of the current trial landscape. As of April 2026, this covers several dozen trials across phases and statuses.

Understanding this landscape took a bit of time. Phase I trials test safety in small populations. Phase II adds preliminary efficacy data. Phase III trials are the large, randomized, controlled studies that regulatory agencies use to make approval decisions. NCT07221292 is Phase III, which means it has already cleared the safety and preliminary efficacy bar established by IntraBio's earlier work in Niemann-Pick type C and Ataxia-Telangiectasia. For a patient family, that matters considerably: you're not enrolling in something with an unknown safety profile.

The other thing worth understanding about ClinicalTrials.gov data is what it doesn't tell you. Trial records are submitted and updated by sponsors, not by the registry itself. A trial listed as "Recruiting" may be actively enrolling or may have a frozen enrollment that hasn't been updated in the registry. Contact information for sites is often incomplete. The start date listed may be an estimate. None of this makes the data unusable, but it means the right call to action is always "contact the trial coordinator directly" rather than "you are eligible, proceed." TrialNavigator is built around this principle: it lowers the barrier to finding the right conversation, not to replacing it.

The frontend is React, deployed on Vercel. The backend is Python with SQLite, running on a GitHub Actions weekly cron. No paid infrastructure is required; the total cost at the scale TrialNavigator will operate is zero dollars per month.

The ClinicalTrials.gov REST API v2 is documented at clinicaltrials.gov/data-api/api. The base query endpoint is /api/v2/studies with query parameters for condition and keyword. Each response contains the trial's identification module (NCT ID, title), status module (overall status, dates), eligibility module (free-text criteria, age range, sex), contacts and locations module (site names, cities, contact emails), and description module (brief summary, detailed description). The updater.py script runs all four queries, deduplicates on NCT ID, and stores normalized records in SQLite. It also diffs against the previous week's records to generate a change digest: new trials, status changes, and new site additions. This digest is written to public/update_digest.json and committed back to the GitHub repo via the Actions workflow, where the frontend can serve it to subscribed users.

Geographic distance is a practically significant feature in rare disease trial matching. For conditions affecting tens of thousands of patients nationally, the nearest enrolling site might be five hundred miles away. TrialNavigator computes site distances using the Haversine formula, which gives great-circle distance between two latitude/longitude points on a sphere:

a = sin²(Δlat/2) + cos(lat₁)·cos(lat₂)·sin²(Δlon/2) d = 2R·arcsin(√a)

where R = 3958.8 miles (Earth's mean radius). This is implemented from scratch in src/utils/geo.js. User zip codes are geocoded to approximate coordinates using the US Census Geocoder, which is free and covers all US zip codes. The driving time estimate is a rough heuristic: approximately 60 mph for distances over 50 miles. It is labeled as an estimate in the UI. Sites are sorted by this distance. For rare disease trials, travel support is often available and worth asking about; the site detail view flags this where disclosed in the trial record.

The plain-language translation of eligibility criteria is the other technically interesting backend component. Raw ClinicalTrials.gov eligibility text is written in regulatory language: "Participants who have received prior treatment with an investigational CACNA1A-targeted therapy within 90 days of screening are excluded." The system prompt for translation is: "Translate the following clinical trial eligibility criterion into plain language that a patient or family can understand without medical training. Be specific and concrete. Maximum 2 sentences." This is called per-criterion via the Claude API (Haiku model, for cost efficiency at scale), and both the original and translated versions are stored. If no API key is configured, the original criterion text is displayed as a fallback.

The eligibility checker is a five-step wizard: age, confirmed diagnosis, CACNA1A variant, current medications, and results. The assessment logic runs in src/utils/eligibility.js.

For each active recruiting trial, three criteria are checked sequentially. Age is assessed against the trial's minimum and maximum age fields extracted from the eligibility module. Diagnosis is a user self-report; if the answer is No, the trial receives a RED indicator and the user is directed to pursue genetic confirmation as a prerequisite. Variant matching uses a lookup table derived from published CACNA1A variant classifications: R192Q, S218L, T666M, and others map to FHM1 (gain-of-function); G293R, F1490K and others map to EA2 (loss-of-function). If the user's variant maps to a phenotype explicitly listed in the trial's conditions, the indicator is GREEN. If the variant is unknown, the indicator is YELLOW with a note to contact the coordinator. If there is a mismatch, it is RED.

The traffic-light framework is deliberate. Clinical trial eligibility assessment requires a physician's judgment and a full review of the trial protocol; TrialNavigator cannot and should not replicate that. What it can do is give a patient a starting point: "Based on your age and R192Q variant, this trial looks like it might be worth a call." A RED result does not mean you are ineligible; it means one criterion on its face looks like a mismatch. The system explicitly avoids framing results as screening-out decisions, and the UI instruction for RED and YELLOW results is consistently "contact the trial coordinator to discuss eligibility."

The variant lookup table is a simplified version of what a full TraitMap integration would provide. Once TraitMap is complete within the MiSOF framework, TrialNavigator can be updated to pull phenotype classification dynamically rather than from a hard-coded lookup. The current table covers the most clinically significant FHM1 GoF variants and the most common EA2 LoF variants; it is documented in src/utils/eligibility.js and straightforward to extend.

N-Acetyl-L-Leucine (levacetylleucine, IB1001) is a modified amino acid developed by IntraBio Inc. It has completed pivotal Phase III trials for Niemann-Pick disease type C and Ataxia-Telangiectasia, both with positive results and established safety profiles. In February 2026, the EMA issued a positive opinion recommending orphan medicinal product designation for levacetylleucine for CACNA1A disorders. The Phase III CACNA1A trial (NCT07221292) is a multinational, randomized, double-blind, placebo-controlled crossover study enrolling patients age 4 and older.

The mechanism is investigational but biologically plausible for FHM1. GoF CACNA1A mutations (R192Q being the most studied) increase calcium influx through Cav2.1 channels, contributing to neuronal hyperexcitability and downstream cortical spreading depression. Levacetylleucine is proposed to improve lysosomal calcium sequestration, reducing intracellular calcium dysregulation. Whether this translates to clinical benefit in FHM1 is what the trial is designed to determine; the prior positive results in two other neurological excitability disorders justify the hypothesis.

The crossover design is clinically and practically important for patient families. In a traditional randomized controlled trial, half the participants receive placebo for the entire study duration. In a crossover design, each participant receives both active drug and placebo in sequence, separated by a washout period. For NCT07221292, this means two 12-week periods: everyone receives levacetylleucine at some point. The trial is also compatible with current medications, meaning patients who are already on topiramate, amitriptyline, or other preventives can enroll without discontinuing their regimen. The route of administration is oral: a granule sachet dissolved in water or juice. These features substantially lower the practical barrier to participation.

TrialNavigator's dedicated page for NCT07221292 includes plain-language answers to the questions families actually ask: can I stay on my medications, what if I get placebo, is this a cure, how do I express interest before enrollment opens. The contact for IntraBio is ccfields@intrabio.com. Once TrialNavigator is deployed, IntraBio will receive a notification that an independent patient-facing tool is directing CACNA1A families to their trial. This costs nothing and puts the project on their radar for future collaboration.

Building the tool is the easier half. Getting it in front of the families who need it is the other half, and the CACNA1A Foundation is the only realistic path to that at scale.

The Foundation's patient community is the largest organized group of CACNA1A families that exists. They have conference attendees, natural history study enrollees, an email list, and researcher relationships. Their current trial listing is a manually maintained webpage. TrialNavigator offers them something better: an automated, continuously updated, patient-readable tool that replaces their manual listing and improves on it substantially. 

The ask is specific: embed TrialNavigator on cacna1a.org, or link to it prominently from the trials section. The tool is open-source on GitHub (axshoe/trialnavigator), free to use, and requires no maintenance from the Foundation. 

The broader observation about what this kind of tool represents is worth stating plainly. Every methodological piece of TrialNavigator was available before I built it. The ClinicalTrials.gov API has existed since 2012. Haversine distance calculation has a closed-form solution. Plain-language translation is a standard API call. The variant-to-phenotype lookup is a table that anyone with access to the FHM1 literature could construct in an afternoon. The contribution is not technical novelty. It is that someone connected these pieces together, pointed them at a specific patient population, and made the result publicly accessible and automatically maintained. In rare disease research, this kind of infrastructure work matters in proportion not to its computational sophistication but to how many people it reaches.